Glycosylation is a very important posttranslational modification of many biologically relevant molecules. A change in the structure of glycans added to glycoproteins and glycolipids is a common feature of the change to malignancy. With the cloning of many of the glycosyltransferases and the identification of specific target molecules, it is now possible to define these changes at the molecular level and to dissect the mechanisms involved. Within the mammary gland, mucin-type O-linked glycosylation has been studied most extensively. In normal resting, pregnant and lactating breast, mucin O-glycans are largely extended (core 2 type) structures. In contrast, mucin O-glycans found in breast carcinomas are often truncated (core 1 type). One mechanism that is responsible for this increase in core 1 structures is a change in the expression of glycosyltransferases, particularly an increase in the expression of the sialyltransferase, ST3Gal-I. The loss, at least to some degree, of core 2 based glycans is a consistent feature of MUC1 mucin when it is expressed by mammary tumours as demonstrated by the unmasking of the SM3 epitope in greater than 90% of breast carcinomas.

O-linked glycosylation in the mammary gland: changes that occur during malignancy.

Cancer Vaccines and Carbohydrate Epitopes

The Thomsen-Friedenreich antigen has been implicated as a cancer-associated antigen in some human organs including the colon Most previous studies of Thomsen-Friedenreich antigen expression in the colon used peanut agglutinin (PNA) to identify the immunodeterminant in tissues However, evidence from other organs suggests that anti-T antibodies have specificities which differ from those of peanut lectin To elucidate the nature of the T-immunodeterminant in colonic mucosa, we compared staining by PNA to that of a polyclonal (PAb) and monoclonal (MAb) anti-T antibody PNA demonstrated the best sensitivity (91%) in cancer tissues but the lowest specificity (68%) in normal mucosa Staining with MAb was only 76% sensitive but 100% specific Sensitivity and specificity of PAb were intermediate between PNA and MAb MAb stained fewer adenomatous polyps than either PNA or PAb, but staining appeared to correlate with premalignant features of the polyps PNA-binding sites were more prevalent than either PAb or MAb in hyperplastic polyps Cell cytoplasm was stained by both antibodies more often than by PNA The majority of fetal colonic specimens stained with all three reagents suggesting that Thomsen-Friedenreich antigen may be an oncodevelopmental antigen in human colon Differences in staining patterns in some tissues may be due to different antigenic specificities among PNA, PAb, and MAb

https://cancerres.aacrjournals.org/content/canres/46/9/4841.full.pdf

Comparison of T-antigen expression in normal, premalignant, and malignant human colonic tissue using lectin and antibody immunohistochemistry.

Early diagnosis of breast cancer

Immunoreactive T and Tn antigens in malignancy: role in carcinoma diagnosis, prognosis, and immunotherapy.

We report here sensitive and specific measurement of immune responses of patients with certain kinds of carcinoma toward the physically and chemically well defined T antigen isolated from healthy human erythrocytes. Over 90% of adenocarcinoma tissues tested possess T-specific immunoreactive structures as determined withhuman antisera, in contrast to healthy tissues and benign lesions. Adenocarcinoma patients recognize the carcinoma-associated T antigen as foreign. Delayed-type skin hypersensitivity reaction to T antigen (DTHR-T) was positive in all 25 lung adenocarcinoma patients tested, in 88% of 101 patients with ductal, in 43% of 30 patients with lobular or tubular breast carcinoma and in 9/9 patients with adenocarcinoma of body cavities. Patients of all Stages reacted positively. All 7 patients with small cell lung carcinoma and 3/5 with malignant melanoma had a positive DTHR-T. None of 17 patients with malignant brain tumors, leukemia or Hodgkin's disease, sarcoma or thyroid carcinoma reacted. The DTHR-T was specific in that all 77 healthy persons and 48/49 with other diseases, including 23/24 with non-cancer lung disease were negative; one patient with organizing interstitial pneumonitis was positive. This points to a possible source of false positive reactions. 91% of 149 patients with histologically benign breast disease had a negative DTHR-T; the histology of some of the positive ones was reexamined, 2 proved to have carcinoma in situ.

Patients' immune response to breast and lung carcinoma-associated Thomsen-Friedenreich (T) specificity.

T antigen, a tumor marker against which breast, lung and pancreas carcinoma patients mount immune responses.

Further studies on the detection of early lung and breast carcinoma by T antigen.

RESPONSES OF PATIENTS TO THEIR CARCINOMA-ASSOCIATED T AND Tn-SPECIFIC ANTIGENS

The usefulness of T antigen in the diagnosis of lung cancer (LCA), including early, was assessed by determining the in vitro delayed type hypersensitivity response to T(DTHR-T), and by measuring with a solid phase immunofluorescent assay the serum anti-T IgM response. Sensitivity of DTHR-T was 89% for 73 patients with LCA including 8/9 with Stage T1N0M0 disease, overall specificity was 95% for 212 healthy persons and those with non-CA disease. The humoral immune assay detected 31/35 (89%) LCA patients including 4/5 Stage T1N0M0 patients. Overall specificity was >90% among 116 persons without CA.

W. A. Fry

Papers

Patients' immune response to breast and lung carcinoma-associated Thomsen-Friedenreich (T) specificity.

T antigen, a tumor marker against which breast, lung and pancreas carcinoma patients mount immune responses.

Further studies on the detection of early lung and breast carcinoma by T antigen.

RESPONSES OF PATIENTS TO THEIR CARCINOMA-ASSOCIATED T AND Tn-SPECIFIC ANTIGENS

Lung cancer patients' autoimmune responses to thomsen-friedenreich (T) antigen: Diagnostic utility