Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas.
Schultheis Anne M,Ng Charlotte K Y,De Filippo Maria R,Piscuoglio Salvatore,Macedo Gabriel S,Gatius Sonia,Perez Mies Belen,Soslow Robert A,Lim Raymond S,Viale Agnes,Huberman Kety H,Palacios Jose C,Reis-Filho Jorge S,Matias-Guiu Xavier,Weigelt Britta
Journal of the National Cancer Institute
Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other.
Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.
Anglesio Michael S,Wang Yi Kan,Maassen Madlen,Horlings Hugo M,Bashashati Ali,Senz Janine,Mackenzie Robertson,Grewal Diljot S,Li-Chang Hector,Karnezis Anthony N,Sheffield Brandon S,McConechy Melissa K,Kommoss Friedrich,Taran Florin A,Staebler Annette,Shah Sohrab P,Wallwiener Diethelm,Brucker Sara,Gilks C Blake,Kommoss Stefan,Huntsman David G
Journal of the National Cancer Institute
Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination.
Synchronous endometrioid carcinoma of the uterine corpus and ovary. A case report and review of the literature.
Grammatoglou X,Skafida E,Glava C,Katsamagkou E,Delliou E,Vasilakaki Th
European journal of gynaecological oncology
Synchronous endometrioid carcinoma of the uterine corpus and ovary is an uncommon but well recognized event. Diagnosis as either a separate independent primary or as a metastatic tumor requires careful consideration of a number of gross and histological features. These features illustrate the criteria helpful in distinguishing independent primaries from metastatic carcinomas which have a different therapeutic implication. The possible link between fertility drugs and carcinogenesis still remains controversial. We report a case of a 52-year-old woman who came to our hospital with a cystic left ovarian mass (8 cm). Hysterectomy and bilateral salpingo-oophorecromy were carried out. Histological examinations showed well differentiated endometrioid ovarian cancer and well differentiated endometrioid endometrial cancer. The endometrial tumor was intramucosal without myometrial or vascular invasion and was associated with atypical complex hyperplasia. The woman had not been previously treated with ovulation induction drugs. She was free of recurrence two years after surgery. Patients with synchronous endometrioid tumors of the endometrium and ovary are generally younger than reported for either endometrial adenocarcinomas or ovarian adenocarcinomas. They tend to be low grade and early stage and are frequently associated with endometriosis. The prognosis of endometrioid type carcinomas is better than other histological types of carcinoma.
Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies.
Perrone Anna Myriam,Girolimetti Giulia,Procaccini Martina,Marchio Lorena,Livi Alessandra,Borghese Giulia,Porcelli Anna Maria,De Iaco Pierandrea,Gasparre Giuseppe
International journal of molecular sciences
In the event of multiple synchronous gynecological lesions, a fundamental piece of information to determine patient management, prognosis, and therapeutic regimen choice is whether the simultaneous malignancies arise independently or as a result of metastatic dissemination. An example of synchronous primary tumors of the female genital tract most frequently described are ovarian and endometrial cancers. Surgical findings and histopathological examination aimed at resolving this conundrum may be aided by molecular analyses, although they are too often inconclusive. High mitochondrial DNA (mtDNA) variability and its propensity to accumulate mutations has been proposed by our group as a tool to define clonality. We showed mtDNA sequencing to be informative in synchronous primary ovarian and endometrial cancer, detecting tumor-specific mutations in both lesions, ruling out independence of the two neoplasms, and indicating clonality. Furthermore, we tested this method in another frequent simultaneously detected gynecological lesion type, borderline ovarian cancer and their peritoneal implants, which may be monoclonal extra-ovarian metastases or polyclonal independent masses. The purpose of this review is to provide an update on the potential use of mtDNA sequencing in distinguishing independent and metastatic lesions in gynecological cancers, and to compare the efficiency of molecular analyses currently in use with this novel method.
Clinical analysis of synchronous primary neoplasms of the female reproductive tract.
Tong Seo-Yun,Lee Yong-Sek,Park Jong-Sup,Bae Seog-Nyeon,Lee Jun-Mo,Namkoong Seung-Eun
European journal of obstetrics, gynecology, and reproductive biology
OBJECTIVES:In this study, a histopathologic review of synchronous primary neoplasms including gynecologic malignancies is presented, and the possible correlation among discrete tumor subsets, natural history, and survival is evaluated. METHODS:Between the years 2000 and 2005, 20 patients suffering from synchronous primary cancers of gynecologic malignancy were identified. Clinical and pathologic information was obtained from medical records. Kaplan-Meier survival analyses were conducted. RESULTS:Patients with synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasm was ovarian cancer coexistent with endometrial cancer (40%). The mean age of patients suffering from synchronous ovarian and endometrial cancer was 45.2 years. All patients with synchronous primary genital malignancies underwent hysterectomy with bilateral salpingo-oophorectomy and/or adjuvant therapy. The mean duration of survival was 57 months (S.E.: 10.0; 95% confidence interval: 37-77). CONCLUSION:Patients suffering from primary genital malignancies are sometimes co-afflicted with other primary cancers. Synchronous ovarian and endometrial cancer constitutes the most common of these cases, and is detected at a relatively early age, with generally favorable prognoses.
Synchronous primary endometrial and ovarian cancer with three different histologic patterns: A case report.
Ree Y-S,Cho S-H,Kim S-R,Cho S-H,Kim K-T,Park M-H
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
Synchronous cancers involving both endometrium and ovary in the female genital tract is a well-recognized phenomenon. However, most of them are metastatic lesions arising from one organ and simultaneous primary cancer occurring in both organs is relatively rare. We report a case with dual primary cancer occurring in both ovaries and endometrium with three different histologies. Recently, a 46-year-old women presented with vaginal bleeding was found to have FIGO stage IC clear cell carcinoma of the left ovary, stage IA borderline mucinous cystadoma of the right ovary, and stage IB endometrial carcinoma of endometrioid type. We present this case with a brief review of references.
Coexisting ovarian malignancy in young women with endometrial cancer.
Walsh Christine,Holschneider Christine,Hoang Yen,Tieu Khai,Karlan Beth,Cass Ilana
Obstetrics and gynecology
OBJECTIVE:In premenopausal women with endometrial cancer, ovarian preservation may be a consideration. Our objective was to examine the occurrence of coexisting ovarian malignancy and to identify predictors of adnexal involvement. METHODS:With institutional review board approval, a retrospective chart review was conducted of young women with endometrial cancer identified at 4 affiliated institutions from 1996 to 2004. RESULTS:Among 102 young women (aged 24-45 years) who underwent hysterectomy for endometrial cancer, 26 (25%) were found to have coexisting epithelial ovarian tumors: 23 were classified as synchronous primaries, and 3 as metastases. Ovarian cancer histology was endometrioid in 92% of cases. Among the 26 cases of coexisting ovarian involvement, 12 (46%) had grade 1 endometrial cancer on preoperative biopsy, 4 (15%) had normal preoperative imaging of the adnexa, and 4 (15%) had benign-appearing ovaries at the time of intraoperative assessment. On final pathology, 18 of 26 cases (69%) occurred in patients with grade 1 endometrial cancers, and 15 (58%) occurred with inner myometrial invasion. Our study further highlights the risk of conservative management with 1 case of ovarian cancer diagnosed 9 months after hysterectomy with ovarian conservation for a stage IA, grade 1 endometrial cancer and a case of advanced endometrial cancer metastatic to the ovaries developing 3 years after successful resolution of a grade 1 endometrial cancer treated with megestrol acetate (Megace). CONCLUSION:Careful preoperative and intraoperative assessment of the adnexa is mandatory in young women with endometrial cancer. Those who desire ovarian preservation should be counseled regarding the high rate of coexisting ovarian malignancy.
Comparison and analysis of the clinicopathological features of SCEO and ECOM.
Wang Ting,Zhang Xiaodan,Lu Zhiying,Wang Junyan,Hua Keqin
Journal of ovarian research
OBJECTIVE:The aim of our study was to evaluate and compare the differences in the clinicopathological variables and overall survival (OS) of synchronous primary cancers of the endometrium and ovary (SCEO) and endometrial cancer with ovarian metastasis (ECOM). In addition, we aimed to determine the characteristics of and effective treatments for patients with SCEO to avoid misdiagnosis and overtreatment. MATERIALS AND METHODS:A review of medical records from January 2009 to January 2017 revealed 111 patients with coexisting ovarian and endometrial carcinoma diagnosed at the Obstetrics and Gynecology Hospital of Fudan University. Clinicopathological variables were analysed using the Chi square test and Student's t test. The survival rate was estimated using the Kaplan-Meier method, and statistical significance was analysed using the logarithmic rank test (univariate analysis). RESULTS:There were 51 cases of SCEO and 60 cases of ECOM. The mean age at diagnosis was 53.96 years and 55.41 years, respectively. There were no differences in age, menopausal status, BMI, CA125 level or complaints between the two groups. The 5-year survival rates were 58.8 and 36.7%, respectively (P < 0.001). Significant differences were found in the endometrial tumour classification, ovarian cancer stage, and lymph node and omentum metastasis between SCEO and ECOM. CONCLUSIONS:The differences found between SCEO and ECOM are of great clinical significance. Our results reveal useful prognostic and clinicopathological features. More aggressive therapies should be administered to both SCEO and ECOM patients, especially elderly patients and those with menopause, endometrial tumours, advanced omentum metastasis, and lymph node dissection.
[Synchronous primary cancers of the endometrium and ovary: review of 43 cases].
Ma Shao-Kang,Zhang Hong-Tu,Sun Yang-Chun,Wu Ling-Ying
Zhonghua zhong liu za zhi [Chinese journal of oncology]
OBJECTIVE:To investigate the clinical and pathological characteristics, treatment methods, and prognosis of synchronous primary cancers of the endometrium and ovary. METHODS:The clinical data of 43 patients with synchronous primary cancers of the endometrium and ovary were retrospectively reviewed. The survival was calculated by Kaplan-Meier method and compared using the log-rank test. RESULTS:The median age at diagnosis was 49 years (range, 28-73 years). The most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and enlarged corpus in 27.9% at physical examination, while pelvic masses were found in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in 23.3% (10 cases) during ultrasound examination. Of 25 patients examined by CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All 15 patients who underwent endometrial biopsies were proven to have endometrial carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases; Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases, III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12 patients had pelvic lymph node dissection. Thirty-eight of the 43 patients (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant ovarian histology was endometrioid or mixed tumor with endometrioid components (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had radiation alone and the remaining 4 cases received no adjuvant treatment. The 3- and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3- and 5-year survival rates of patients with both endometrioid and ovarian carcinomas were higher than that of those with non-endometrioid or mixed subtypes (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients with early stage disease were better than those of the other patients (93.3%, 93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was showed by univariate analysis that lower CA125 level, early FIGO stage, and adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5-year survival rates, while only early FIGO stage and chemotherapy plus radiotherapy were revealed by multivariate analysis as independent prognostic factors. CONCLUSION:Synchronous primary cancers of the endometrium and ovary are different from either primary endometrial carcinoma or ovarian cancer, while it can usually be detected in early stage and with a good prognosis. The impact of the CA125 level on prognosis needs to be further studied. Surgical treatment alone may be enough for early stage patients. Chemotherapy plus radiotherapy may be necessary for advanced stage patients.
Characteristics and prognosis of coexisting adnexa malignancy with endometrial cancer: a single institution review of 51 cases.
Chen Lu,Zhao Qiang,Lv Xiaojuan
Archives of gynecology and obstetrics
OBJECTIVE:To explore and compare the differences in the clinicopathological characteristics and prognosis of synchronous primary endometrial and ovarian cancers with primary endometrial cancer metastatic to adnexa. MATERIALS AND METHODS:Between January 1997 and December 2009, 51 cases with endometrial cancer simultaneously with adnexa malignancy were identified. Among them, there were 18 cases with synchronous primary cancers of the endometrium and ovary (Group A) and 33 cases with primary endometrial cancer metastatic to the adnexa (Group B). Clinical and pathologic information was obtained from medical records. Parametric methods were used to compare clinical and pathologic features. Kaplan-Meier survival analysis was performed and compared using log-rank test. RESULTS:The mean age at diagnosis of the disease was 56.6 ± 10.8 years (range 34-76 years) in Group A and 53.1 ± 9.5 years (range 37-76 years) in Group B. The two groups' distribution of preoperative image findings, size of endometrial lesion, myometrial invasion, unilateral or bilateral, cervix invasion, and postoperative radiation existed significant differences. With a mean follow-up time of 4.3 ± 3.4 years (range 2-11 years), 5-year overall survival (OS) was 75 and 56% in Groups A and B, respectively (p = 0.034). The univariate analysis showed only postoperative radiation and synchronous tumors were independent factors which affected OS (p = 0.015; p = 0.034) and progression-free survival (PFS) (p = 0.015; p = 0.036), respectively. Not any feature was revealed by multivariate analysis as independent prognostic factors. CONCLUSION:Our results showed that OS and PFS of synchronous primary ovarian cancer in patients with endometrial cancer is better than those with ovarian metastasis patients. Pre- and intra-operative, intensive and careful assessment, and strict and continuous postoperative surveillance should pay attention to the endometrial cancer patients who preserved ovary for having possibility of coexisting occult ovarian lesions.
Clinicopathological characteristics of patients with synchronous primary endometrial and ovarian cancers: A review of 43 cases.
Liu Yuantao,Li Jun,Jin Hongyan,Lu Ying,Lu Xin
Synchronous primary endometrial and ovarian cancers are uncommon. The purpose of this study was to evaluate the clinicopathological characteristics, treatment and prognosis of synchronous primary endometrial and ovarian cancers. The clinicopathological characteristics of 43 patients with synchronous primary endometrial and ovarian cancers in the Obstetrics and Gynecology Hospital of Fudan University between 1999 and 2009 were retrospectively reviewed. Our results revealed that the median age at the time of diagnosis was 51 years (range, 29-71). The common presenting symptoms were abnormal uterine bleeding (AUB, 65.12%), abdominal mass (25.58%), abdominal pain and abdominal fullness (39.53%). An elevated CA125 level was observed in the majority of patients (n=20, 76.9%). Endometrioid type accounted for 60.47% of uterine carcinomas and different pathological types, including serous adenocarcinoma, clear cell carcinoma, adenosquamous and acanthoadenocarcinoma, were also identified in synchronous primary endometrial and ovarian cancers. All patients underwent surgical intervention (hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy or debulking surgery). The 5-year survival rate was 86.05% and nine patients had recurrence (20.93%). The early stage group (FIGO stages I and II) had more favorable prognosis than the advanced stage group (FIGO stages III and IV; P<0.05). In conclusion, synchronous primary endometrial and ovarian cancers are different from either primary endometrial carcinoma or ovarian cancer and are usually identified at early stages with a good prognosis.
Synchronous Primary Cancers of the Endometrium and Ovary With the Same Histopathologic Type Versus Endometrial Cancer With Ovarian Metastasis: A Single Institution Review of 72 Cases.
Bese Tugan,Sal Veysel,Kahramanoglu Ilker,Tokgozoglu Nedim,Demirkiran Fuat,Turan Hasan,Ilvan Sennur,Arvas Macit
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
OBJECTIVE:The purpose of this study was to evaluate the clinicopathological characteristics and survival outcomes of women with simultaneous endometrial and ovarian carcinomas having the same histopathologic type. MATERIALS AND METHODS:A review of medical records from 1997 to 2015 identified 72 patients with simultaneous carcinomas of the endometrium and ovary with the same histopathologic type. Patients with synchronous primary cancers of endometrium and ovary (SCEOs) were compared with patients with primary endometrial cancer with ovarian metastasis (ECOM). Clinical and pathological data were obtained from the patients' medical records. Clinicopathological variables including categorical data were analyzed by χ(2) or Fisher exact test and continuous data by a Student t test. A Kaplan-Meier survival analysis was performed and compared by using the log-rank test. RESULTS:A univariate and multivariate analysis of 72 patients with SCEO with the same histopathologic type revealed that SCEO is an independent prognostic factor of 10-year overall survival. There were 31 patients in the SCEO group and 41 patients in the ECOM group. With a mean follow-up time of 68.2 months, the 10-year overall survival rates were 61.3% and 36.6% in SCEO and ECOM groups, respectively (P = 0.029). Age, menopausal status, stage of ovarian cancer, performing lymphadenectomy, grade of endometrial tumor, omental metastasis, and residual tumor were found to be significant risk factors for recurrence in the synchronous group. CONCLUSIONS:The differentiation between SCEO and ECOM is of great clinical importance while our results showed a better prognosis for patients with SCEO compared with patients with ECOM. More aggressive therapeutic approaches may be considered for patients with SCEO who are older, postmenopausal, and/or have advanced grade of endometrial tumor, omental metastasis, and residual tumor. Lymphadenectomy should be performed in every patient with SCEO.
Clinicopathological Characteristics and Prognostic Factors of Synchronous Endometrial and Ovarian Cancers-A Single-Institute Review of 43 Cases.
Jain Vandana,Sekhon Rupinder,Pasricha Sunil,Giri Shveta,Modi Kanika Batra,Shrestha Eliza,Ram Dharma,Rawal Sudhir
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
OBJECTIVES:The objectives of our study were to demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary cancers of the endometrium and ovary. METHODS:A retrospective analysis of 43 pathologically proven cases of synchronous primary endometrial and ovarian cancers diagnosed between January 2005 and December 2015 was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline tumors, and nonepithelial tumors of the ovary and patients who received neoadjuvant chemotherapy were excluded from the study. Disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis to determine independent prognostic factors was performed using the Cox regression model. RESULTS:Mean age at diagnosis was 48.49 years. The most common presenting symptom was abnormal uterine bleeding in 58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients (30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%) were premenopausal; 76.7% of the patients received adjuvant treatment after surgery. Mean follow-up period was 48.9 months. Twelve patients developed recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118-month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3 disease for both endometrial and ovarian cancers and presence of lymphovascular space invasion were associated with significantly worse 118-month DFS and OS, respectively. CONCLUSIONS:Women with synchronous primary endometrial and ovarian cancers are young, nulliparous, obese, and premenopausal and have a favorable overall prognosis. Grade 3 disease at both sites and presence of lymphovascular space invasion are independent prognostic factors for recurrence and survival, respectively.
Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature.
Dębska-Szmich Sylwia,Czernek Urszula,Krakowska Magdalena,Frąckowiak Marta,Zięba Agnieszka,Czyżykowski Rafał,Kulejewska Dominika,Potemski Piotr
Przeglad menopauzalny = Menopause review
Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%). Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients). The range of the patients' age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 - II, and 2 - III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months). One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.
Synchronous primary endometrial and ovarian cancers: a multicenter review of 63 cases.
Solmaz Ulas,Karatasli Volkan,Mat Emre,Dereli Levent,Hasdemir Pinar Solmaz,Ekin Atalay,Gezer Cenk,Sayhan Sevil,Sanci Muzaffer,Guvenal Tevfik
AIMS:To investigate clinicopathologic characteristics, therapeutic methods, and prognostic factors in women with synchronous primary endometrial and ovarian cancers (SEOCs). METHODS:A retrospective review of 2 cancer registry databases in Turkey was conducted to identify patients diagnosed with SEOCs between January 1995 and December 2012. Patients with recurrent, metastatic, and metachronously occurring tumors were excluded. Multivariate logistic regression models were used to identify prognostic predictors for progression-free survival (PFS) and overall survival (OS). RESULTS:The analysis included 63 women with SEOCs. Seventy-six percent of the patients had stage I endometrial cancer, and 60% of the patients had stage I ovarian cancer. Thirty-seven patients (58.7%) had endometrioid/endometrioid histology. Optimal cytoreduction was obtained in 47 (74.6%) patients. Recurrence developed in 17 patients (27%). Multivariate analysis confirmed lymphovascular space invasion (LVSI) as an independent poor prognostic factor for OS (odds ratio [OR] 3.1, p = 0.045), whereas early-stage disease and optimal cytoreduction were found to be independent good prognostic factors for both PFS (OR 12.85, p<0.001 and OR 4.58, p = 0.004, respectively) and OS (OR 7.31, p = 0.002 and OR 2.95, p = 0.028, respectively). The 3- and 5-year OS rates were 74% and 69%, respectively. CONCLUSIONS:Our study demonstrated that optimal cytoreduction, early-stage disease, and LVSI are the most significant factors affecting survival in women with SEOC.
Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature.
Dogan Askin,Schultheis Beate,Rezniczek Günther A,Hilal Ziad,Cetin Cem,Häusler Günther,Tempfer Clemens B
BACKGROUND:Young women with endometrial cancer (EC) have an increased risk of synchronous ovarian cancer. The prognosis of women with synchronous endometrial and ovarian cancer (SEOC) is good. A high proportion of affected women have hereditary non-polyposis colon cancer syndrome (HNPCC). CASE PRESENTATION:We present the case of a 45-year-old woman with histologically proven endometrioid adenocarcinoma of the endometrium (pT1B, G2, R0 without lymphovascular space invasion). She underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Final histology revealed a synchronous bilateral endometrioid ovarian cancer (pT1A, G2, R0). HNPCC analysis by immunohistochemistry showed no microsatellite instability in MSH2, MSH6, MLH1, and PMS2. No adjuvant therapy was administered, clinical follow-up with regular gynecological examinations was recommended. In a systematic literature review, 2,904 cases of women with SEOC were identified with 1,035 (36%) of them being premenopausal or <50 years of age. The proportion of women with SEOC among all reported EC cases was 842/23,498 (3%) and the proportion of young women with SEOC among all reported EC cases was 261/23,498 (1%). In summary, microsatellite instability and subsequent mutations in mismatch repair genes compatible with HNPCC were identified in 6/15 (40%) women analyzed. The mean recurrence-free and overall survival times of young women with SEOC were 1.9 (min 0.2, max 3) and 4.0 (min 0.2, max 22.1) years, respectively. CONCLUSION:Young women with EC have a high risk of synchronous ovarian cancer. Thus, in young women with EC, bilateral salpingo-oophorectomy or careful histological assessment of both ovaries are recommended in order to confirm or rule out SEOC. HNPCC testing should be offered to all women.
Synchronous Primary Endometrial and Ovarian Cancers: Trends and Outcomes of the Rare Disease at a South Asian Tertiary Care Cancer Center.
Khalid Nazish,Ullah Faizan,Zafar Hania,Anwer Abdul Wahid,Abbas Taskheer,Shakeel Osama,Faisal Muhammad,Sadaf Tabinda,Syed Aamir Ali
Background and objective The incidence of synchronous primary endometrial and ovarian cancer is uncommon and poses a diagnostic challenge to the treating physician about their origin as either primary or metastasis. The purpose of this study was to evaluate the clinicopathological behavior, treatment modality-related outcomes, and prognosis related to primary endometrial and ovarian cancers at a tertiary care referral center in South Asia. Methods We retrospectively analyzed 30 patients with synchronous ovarian and endometrial cancers treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan from January 2005 to August 2017. Results The median age of the patients at the time of diagnosis was 51 years (range: 25-72 years). The common presenting symptoms were irregular uterine bleeding (30%), post-menopausal bleeding (26.7%), abdominal mass (16.7%), and abdominal pain (26.7%). Endometrial adenocarcinoma type was the most common histological variant found among the participants: 90% (n=27) of uterine and 56.7% (n=17) of ovarian cancers. All patients underwent surgical intervention. Among them, 25 patients received platinum-based adjuvant chemotherapy, four received neoadjuvant chemotherapy, and 18 received adjuvant radiotherapy. The early-stage group [International Federation of Gynecology and Obstetrics (FIGO) stage I and II] had a more favorable prognosis than the advanced stage group (FIGO stages III and IV). Conclusion Based on our findings, patients with synchronous primary endometrial and ovarian cancers have better overall survival rates than patients with single primary ovarian or endometrial cancers. Also, synchronous primary endometrial and ovarian cancer endometroid types have better overall survival than patients with non-endometrioid or mixed histologic types.
Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome.
Reijnen Casper,Küsters-Vandevelde Heidi V N,Ligtenberg Marjolijn J L,Bulten Johan,Oosterwegel Marloes,Snijders Marc P L M,Sweegers Sanne,de Hullu Joanne A,Vos Maria C,van der Wurff Anneke A M,van Altena Anne M,Eijkelenboom Astrid,Pijnenborg Johanna M A
International journal of cancer
Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.
Synchronous primary cancers of endometrium and ovary vs endometrial cancer with ovarian metastasis: an observational study.
Moro F,Leombroni M,Pasciuto T,Trivellizzi I N,Mascilini F,Ciccarone F,Zannoni G F,Fanfani F,Scambia G,Testa A C
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
OBJECTIVE:To compare the ultrasound characteristics of patients with synchronous primary cancers of the endometrium and ovary vs those of patients with endometrial cancer with ovarian metastasis. METHODS:This was a single-institution retrospective observational study of patients with a histological diagnosis of endometrial cancer and an ovarian malignant mass, who had undergone preoperative ultrasound examination at our unit. Based on the histological diagnosis, patients were classified into two groups: those with synchronous primary cancers of the endometrium and ovary (synchronous group) and patients with endometrial cancer with ovarian metastasis (metastasis group). We compared the ultrasound features of ovarian malignant masses and of endometrial cancers between the two groups. Student's t-test, Mann-Whitney U-test, χ test or Fisher's exact test were used for comparisons of variables between the two histological groups, as appropriate. RESULTS:We identified 131 patients, of whom 51 had synchronous primary cancers of the endometrium and ovary (synchronous group) and 80 had endometrial cancer with ovarian metastasis (metastasis group). On ultrasound examination, ovarian masses in the synchronous group were more often multilocular-solid and less often bilateral than those in the metastasis group. With respect to the ultrasound features of the endometrial lesions, the median largest diameter was 29 (range, 11-118) mm in the synchronous group in comparison with 51.5 (range, 6-150) mm in the metastasis group (P < 0.0001). Endometrial lesions in the synchronous group presented more often with no myometrial infiltration and less often with a multiple-vessel pattern on color Doppler compared with the endometrial lesions in the metastasis group. CONCLUSIONS:Synchronous primary cancers of the endometrium and ovary have significantly different sonomorphological patterns compared with endometrial cancer with ovarian metastasis. Ovarian masses in women with synchronous primary cancers of the endometrium and ovary appeared as unilateral multilocular-solid or solid masses, whereas ovarian masses in women with endometrial cancer with ovarian metastasis were mostly bilateral solid masses. The different sonomorphology of these two cancers may facilitate their preoperative identification, helping the surgeon to determine optimum management for the patient. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.
Ishikawa Masako,Nakayama Kentaro,Nakamura Kohei,Ono Ruriko,Yamashita Hitomi,Ishibashi Tomoka,Minamoto Toshiko,Iida Kouji,Razia Sultana,Ishikawa Noriyoshi,Kyo Satoru
Synchronous endometrial and ovarian carcinomas) represent 5% to 10% of endometrial or ovarian carcinomas. We assessed genetic alterations (in PTEN, CTNNB1, POLE, etc) and evaluated correlations with patient outcomes to determine the utility of clonality analyses for differentiating between metastases and concurrent primary tumors and for determining whether genetic alterations in synchronous tumors are predictive of biological behavior. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tissues and frozen tissues from patients with synchronous endometrial and ovarian carcinomas. Samples were obtained from the Department of Obstetrics and Gynecology at the Shimane University School of Medicine between 2003 and 2017. Sanger sequencing was used to analyze the mutational status of the coding exons in TP53, PTEN, POLE, PIK3CA, KRAS, and CTNNB1 using previously published primers. All patients lived, and 3 had disease recurrence. The frequencies of somatic mutations in TP53, PTEN, CTNNB1, KRAS, and POLE were 3 (37.5%), 2 (25.0%), 3 (37.5%), 0 (0.0%), and 5 (62.5%) of 8 cases in ovarian tumors and 3 (37.5%), 2 (25.0%), 3 (37.5%), 1 (12.5%), and 5 (62.5%) of 8 cases in endometrial tumors, respectively. The frequencies of POLE and CTNNB1 mutations were higher than those in previous reports. A clonal relationship was determined by genomic analyses in 3 of 6 cases that were initially diagnosed as primary independent tumors. We confirmed that these 3 cases were indicated metastatic tumors because the lesion of mutation was the same. This information, provided by the sequencing-based strategy, could be useful for hypothesizing a patient's prognosis and deciding on treatment.
Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers.
Kim Soyoun Rachel,Tone Alicia,Kim Raymond,Cesari Matthew,Clarke Blaise,Eiriksson Lua,Hart Tae,Aronson Melyssa,Holter Spring,Lytwyn Alice,Maganti Manjula,Oldfield Leslie,Gallinger Steven,Bernardini Marcus Q,Oza Amit M,Djordjevic Bojana,Lerner-Ellis Jordan,Van de Laar Emily,Vicus Danielle,Pugh Trevor J,Pollett Aaron,Ferguson Sarah Elizabeth
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
OBJECTIVES:For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests. METHODS:30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing. RESULTS:Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium. CONCLUSIONS:There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.