STn antigen tissue expression and its presence in blood were found in various gynecological cancers originating from the ovary, cervix, endometrium and vulva. The transfer of sialic acid in α2,6-linkage to Tn structure usually terminates the further elongation of oligosaccharide. Therefore, sialyl-Tn (sTn, Neu5Acα2-6GalNAcα-O-Ser/Thr,
Figure 1) expression leads to a shortening of
O-glycan chains [
2]. STn displays restricted expression in normal tissues [
72,
92], but can be detected at various frequencies in almost all kinds of carcinomas, even more frequently in adenocarcinomas. At least 25-30% of breast cancers are sTn-positive [
93] and overexpression of sTn occurs in almost 40% of breast cancers [
94]. STn expression was found to be higher in ovarian cancer patients which were associated with shorter survival [
95]. There is increasing evidence that sTn expression is similarly associated with survival in breast cancer [
96,
97,
98,
99], potentially as a short-term outcome [
97]. In node-positive breast cancer patients sTn expression was also correlated with a lack of response to adjuvant chemotherapy [
98]. Using immunohistochemical staining and anti-sTn monoclonal antibody (TKH-2), the disaccharide was detected in a majority of ovarian and cervical cancers with no positive match in remaining cancer types, benign, and normal controls [
79]. A reduced number of tissue sTn positive samples also showed detectable levels of serum sTn. Using the same mAb directed to sTn, another study found detectable levels of sTn in serum of ovarian cancer patients which significantly correlated with increased malignancy, metastatic progression and low patient survival [
100]. An increased sTn expression in ovarian carcinoma cells was detected when primary tumors were compared with metastatic lesions [
101]. Another study of the same investigators, conducted on tissue samples from 45 patients, confirmed that sTn is widely expressed in ovarian carcinomas and related metastases, but could not verify sTn expression to be predictable of disease outcome [
102]. There is a clear indication that sTn expression in tissue and blood serum correlates with tumor progression in breast and ovarian cancer. The mechanisms, underlying the appearance of this
O-glycan in several types of carcinomas is still unknown, as is its varied tissue expression. One possible explanation suggests an increased gene expression of
ST6GalNAc-I glycosyltransferase, the enzyme which transfers sialic acid to Tn antigen, thus creating Neu5Acα2-6GalNAc, which is the sTn epitope [
103]. It has been demonstrated that this is not the case in colon cancer because ST6GalNAc-I activity was not elevated in cancerous colonic tissues as compared to normal mucosa. In contrast, sTn was detected in cancer cells and was absent in normal controls [
104]. The transfection of
ST6GalNAc-I and reconstitution of sTn expression was performed in breast cancer cells and demonstrated that the expression of RNA-encoding
ST6GalNAc-I and the expression of sTn are directly linked [
93]. The discrepancy to observations in colon cancer were explained by reduced sialic acid
O-acetylation, unmasking sTn for mAb recognition [
105]. STn antigen is usually present on
O-glycosylated proteins such as MUC1 [
106], CD44 [
107], and MUC16 [
108]. It has been suggested, that altered glycosylation of these molecules may influence adhesion and migration (motility) of cancer cells. Namely, sTn expression in breast cancer cells is sufficient to modify biological features, decreasing adhesion and increasing migration and tumor growth [
109,
110]. CD44 as the main hyaloronan (nonsulfated glycosaminoglycan) receptor appears to play an important role in mediating the binding of tumors to the extra-cellular matrix (ECM) [
111,
112]. STn as a classical TACA has also been demonstrated to be widely recognized by naturally occurring antibodies not only in cancer patients, but in healthy controls. In a study on 106 healthy donors which investigated the binding to anti-glycan antibodies on a glycan array, high-levels of anti-sTn antibodies were found [
52]. In a study of ours, using the same glycan array, we also observed detectable levels of anti-glycan antibodies to sTn in healthy and non-mucinous ovarian cancer patients without significantly distinguishing these two groups [
24]. In addition, our custom-made suspension array [
48,
67] detected anti-sTn antibodies that significantly correlated with clinico-pathological characteristics of gynecologically investigated samples (data not published). Glycopeptide array incorporating sTn-MUC1
60mer glycopeptides revealed high levels of anti-sTn antibodies significantly associated with reduced incidence and increased time to metastasis in breast cancer patients [
23]. In so far as elevated levels of sTn in breast cancer are associated with poor prognosis, these findings on anti-sTn antibodies suggest their evident role in anti-cancer immune response. Nevertheless, a direct proof showing correlation of anti-sTn antibody levels in patient sera and sTn expression in matched tissue samples is still needed.