Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. Fu C,Zhao H,Wang Y,Cai H,Xiao Y,Zeng Y,Chen H HLA Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment. The unique molecular chaperone of T-synthase is Cosmc, which helps T-synthase to fold correctly in the endoplasmic reticulum. Dysregulation of these glycosyltransferases, molecular chaperones, or the environment is involved in the dysregulation of O-glycans. Tn, sTn, and T antigen neo- or over-expression occurs in many types of cancer including gastric, colon, breast, lung, esophageal, prostate, and endometrial cancer. This review discusses the major synthetic pathway of O-glycans and the mechanism by which Tn, sTn, and T antigens promote tumor metastasis. 10.1111/tan.12900

The detection of microscopically disseminated cancer cells in the abdominal cavity by intraoperative lavage cytology combined with an immunocytochemical method in gastric cancer. Imada T,Rino Y,Cyo H,Oshima T,Hatori S,Wakebe S,Kabara K,Shiozawa M,Takahashi M,Takanashi Y Anticancer research This study was conducted to clarify the possible role of the immunocytochemical examination of intraoperative lavage cytology in gastric cancer. The expression of CA19-9, STN, SLX and CEA in tissues were examined in 70 patients with advanced gastric cancer who underwent gastric resection. The tissue sections were processed with the hematoxylin and eosin staining and immunostaining using the avidin-biotin-peroxidase complex (ABC) method. Fifty one patients underwent the lavage cytology. The cytologic samples were stained by the conventional Papanicolau method and ABC immunocytochemical method. Expression of CEA was detected at obviously higher frequency than those of the 3 carbohydrate antigens. The method combined with 4 antibodies increased the detection rate to 97.2%. Conventional lavage cytology was positive in 16 out of 51 patients. The diagnosis of class III in four patients was changed to class V through the immunocytochemical examination. The immunocytochemical examination of lavage cytology is very useful to verify the microscopically disseminated cancer cells in gastric cancer.

Influence of sialic acid removal on MUC1 antigenic reactivity in head and neck carcinoma. Pathology oncology research : POR To investigate the influence of sialic acid removal on MUC1 peptidic and carbohydrate epitope reactivity in head and neck squamous cell carcinoma (HNSCC), tumor samples belonging to 24 HNSCC patients were studied by standard immunohistochemistry (IHC) with and without desialylation with 0.1 U/ml neuraminidase. From each tumor sample, subcellular fractions were obtained and analyzed by SDS-PAGE and Western blotting (WB). Three monoclonal antibodies (MAbs) were used: C595 MAb directed to MUC1 protein core, an anti-Tn hapten MAb, and an anti-sTn hapten MAb; a comparative analysis between desialylated and sialylated samples was performed. By IHC without neuraminidase treatment, 19 of 24 samples reacted with anti-MUC1 peptidic epitope, while Tn hapten was not detected and sTn was found in 1 of 24 cases. Desialylation increased either the number of reacting cells or the intensity of the reaction with C595 and anti-Tn MAbs, and some negative samples became positive. On the other hand, sTn expression decreased with desialylation. By WB, several bands from >200 to 25 kDa were found; desialylation increased high-molecular-weight bands, diminishing the detection of low-molecular-weight ones. The use of desialylation is a suitable treatment that contributes to the exposure of MUC1-associated epitopes, which may be related to the spreading of HNSCC. 10.1007/BF02893370

Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells: A novel biomarker and an analytical tool for precision oncology applications. Neves Manuel,Azevedo Rita,Lima Luís,Oliveira Marta I,Peixoto Andreia,Ferreira Dylan,Soares Janine,Fernandes Elisabete,Gaiteiro Cristiana,Palmeira Carlos,Cotton Sofia,Mereiter Stefan,Campos Diana,Afonso Luís Pedro,Ribeiro Ricardo,Fraga Avelino,Tavares Ana,Mansinho Hélder,Monteiro Eurico,Videira Paula A,Freitas Paulo P,Reis Celso A,Santos Lúcio Lara,Dieguez Lorena,Ferreira José Alexandre New biotechnology Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metastases hold great potential for liquid biopsies by providing a molecular fingerprint for disease dissemination and its temporal evolution through the course of disease management. CTC enumeration, classically defined on the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and absence of the pan-leukocyte marker CD45, has been shown to correlate with clinical outcome. However, existing approaches introduce bias into the subsets of captured CTCs, which may exclude biologically and clinically relevant subpopulations. Here we explore the overexpression of the membrane protein O-glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but not in blood cells, to propose a novel CTC isolation technology. Using a size-based microfluidic device, we show that the majority (>90%) of CTCs isolated from the blood of patients with metastatic bladder and colorectal cancers express the STn antigen, supporting a link with metastasis. STn CTC counts were significantly higher than EpCAM-based detection in colorectal cancer, providing a more efficient cell-surface biomarker for CTC isolation. Exploring this concept, we constructed a glycan affinity-based microfluidic device for selective isolation of STn CTCs and propose an enzyme-based strategy for the recovery of viable cancer cells for downstream investigations. Finally, clinically relevant cancer biomarkers (transcripts and mutations) in bladder and colorectal tumours, were identified in cells isolated by microfluidics, confirming their malignant origin and highlighting the potential of this technology in the context of precision oncology. 10.1016/j.nbt.2018.09.004