Search

Background: Cancer/testis (CT) antigens are protein antigens normally expressed only in germ cells of testis, and yet are expressed in a proportion of a wide variety of human cancers. CT antigens can elicit spontaneous immune responses in cancer patients with CT-positive cancers, and CT antigen-based therapeutic cancer vaccine trials are ongoing for "CT-rich" tumors. Although some previous studies found breast cancer to be "CT-poor", our recent analysis identified increased CT mRNA transcripts in the ER-negative subset of breast cancer., Methodology/principal Findings: In this study, we performed a comprehensive immunohistochemical study to investigate the protein expression of eight CT genes in 454 invasive ductal carcinomas, including 225 ER/PR/HER2-negative (triple-negative) carcinomas. We found significantly more frequent expression of all eight CT antigens in ER-negative cancers, and five of them--MAGEA, CT7, NY-ESO-1, CT10 and CT45, were expressed in 12-24% of ER-negative cancers, versus 2-6% of ER-positive cancers (p<0.001 to 0.003). In comparison, GAGE, SAGE1 and NXF2 were only expressed in 3-5% of ER-negative and 0-2% of ER-positive cancers. ER-negative cancers were also more likely to simultaneously co-express multiple CT antigens, with 27% (34/125) of ER-negative, CT-positive tumors expressing three or more CT antigens. HER2 status had no consistent effect on CT expression, and triple-negative carcinomas showed similar frequencies of MAGEA and NY-ESO-1 expression as ER-negative/HER2-positive carcinomas. More frequent CT expression was also found in tumors with higher nuclear grade (p<0.001 to p = 0.01) and larger in size (>2 cm)., Conclusions/significance: CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored.

Background: cancer-testis (CT) antigens, frequently expressed in human germline cells but not in somatic tissues, may become aberrantly reexpressed in different cancer types. The aim of this study was to investigate the expression of CT antigens in breast cancer., Patients and Methods: a total of 100 selected invasive breast cancers, including 50 estrogen receptor (ER) positive/HER2 negative and 50 triple negative (TN), were examined for NY-ESO-1 and MAGE-A expression by immunohistochemistry., Results: a significantly higher expression of MAGE-A and NY-ESO-1 was detected in TN breast cancers compared with ER-positive tumors (P = 0.04). MAGE-A expression was detected in 13 (26%) TN cancers compared with 5 (10%) ER-positive tumors (P = 0.07). NY-ESO-1 expression was confirmed in nine (18%) TN tumor samples compared with two (4%) ER-positive tumors., Conclusions: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

Cancer/testis (CT) genes are predominantly expressed in human germ line cells, but not somatic tissues, and frequently become activated in different cancer types. Several CT antigens have already proved to be useful biomarkers and are promising targets for therapeutic cancer vaccines. The aim of the present study was to investigate the expression of CT antigens in breast cancer. Using previously generated massively parallel signature sequencing (MPSS) data, together with 9 publicly available gene expression datasets, the expression pattern of CT antigens located on the X chromosome (CT-X) was interrogated. Whereas a minority of unselected breast cancers was found to contain CT-X transcripts, a significantly higher expression frequency was detected in estrogen and progesterone receptor (ER) negative breast cancer cell lines and primary breast carcinomas. A coordinated pattern of CT-X antigen expression was observed, with MAGEA and NY-ESO-1/CTAG1B being the most prevalent antigens. Immunohistochemical staining confirmed the correlation of CT-X antigen expression and ER negativity in breast tumors and demonstrated a trend for their coexpression with basal cell markers. Because of the limited therapeutic options for ER-negative breast cancers, vaccines based on CT-X antigens might prove to be useful.

The immunocytochemical demonstration, using monoclonal antibodies, of diverse cellular constituents has improved our understanding of many aspects of oncology. This review will focus on this approach to facilitate the detection of human tumors, improve their histological classification and provide functional parameters with potential aetiological, prognostic and/or therapeutic value.

The normal tissue distribution of the antigens recognized by a monoclonal antibody (LICR LON 28/22/23) reacting with a murine teratocarcinoma cell line and the preimplantation mouse embryo is described. The antigen(s) was found to be present in tissues derived from all the germ layers of the embryo, and to be found in the membrane and cytoplasm of cells of different tissues. In stratified and pseudostratified epithelia, of mouse and rat tissues, it was expressed only by the basal cells and it was also found on the myoepithelial cells of the lactating rat breast. In these tissues it could provide a useful marker for carcinogenesis studies.

Carcinoembryonic antigen (CEA), the zinc glycinate marker (ZGM) and epithelial membrane antigen (EMA) have been described as epithelial or tumour markers of varying specificity. These antigens were studied by immunoperoxidase localization in selected cell blocks of 62 pleural or peritoneal effusions and compared to cytological findings and review of the clinical records. By cytological criteria, 25 of the cell blocks were positive for malignancy, 30 negative, and 7 inconclusive. CEA, ZGM, and EMA by immunoperoxidase staining were localized on the cell surface and often in the cytoplasm of malignant cells, in 11/25 (44 per cent), 17/25 (68 per cent) and 22/25 (88 per cent) of the positive cell blocks respectively. Ten (40 per cent) of these cases were positive for all three antigens, 7 (28 per cent) for two, and 6 (24 per cent) for one. Of the 7 cases which were inconclusive on routine cytological reporting, 5 were positive for at least one marker. In 3 of the 5 a diagnosis of malignancy was confirmed, and in the other two was strongly suspected as malignant on clinical grounds. Macrophages were sometimes positive for one or more markers (but showed cytoplasmic staining only) and mesothelial cells in some cases stained positively for EMA but were always negative for CEA and ZGM. Localization of the 3 antigens in cells of malignant effusions was compared with their localization in the primary tumours in 9 cases. Localization corresponded for CEA in 7 of 9 cases, for EMA in 8 of 8 an for ZGM in only 2 of 9. Effusion fluid levels for CEA were compared with the cytological and immunocytochemical findings in 30 cases. Mucin stains performed on the cell blocks were also compared with the immunoperoxidase findings.

Urines of several patients with urothelial carcinomas contain inhibitors of the immunoreaction between carcinoembryonic antigen derived from human colorectal carcinomas and monospecific goat antiserum raised against the antigen. These inhibitors range in approximate molecular weights from less than 1000 to several millions, and two have been isolated by a combination of extraction, gel filtration and electrophoretic procedures. These are respectively a macromolecular aggregate, component UCEA-3, which is excluded by Sepharose 4B, and a glycoprotein(s) component, UCEA-1, with mean molecular weight (2x10(5)) similar to that of carcinoembryonic antigen. Comparison of the properties of component UCEA-1 and carcinoembryonic antigen on gel filtration, electrophoresis, immunoelectrophoresis and density gradient ultracentrifugation indicates that these substances of similar molecular size and net charge differ in some immunochemical properties.

The value of a monoclonal antibody, LICR-LON-Fib-75 (Fib-75), which mediates complement lysis and recognises an antigen present on all epithelial-tumour cells so far studied but not on lymphoid cells or bone-marrow stem cells, in clearing infiltrated bone marrow was assessed. Chromium-51-release and trypan-blue-exclusion assays showed that no tumour cells were viable after exposure to Fib-75 and complement except when large clumps (greater than 500 cells) were present, whereas Fib-75 had no significant effect on bone-marrow cells, as judged by colony-forming-unit and pluripotential-stem-cell assays.

Immunocytochemical methods can be used to demonstrate tumor products and antigens at the cellular level. This approach facilitates the classification of tumors and the detection of small metastatic tumor foci in biopsy material from various sites including the bone marrow.

The concept of tumour-specific antigens is constantly undergoing reappraisal with the development of more sensitive methods for their detection. This has resulted in the finding that the many 'new' antigens produced by human tumours or materials immunologically closely related to them are also present in non-neoplastic tissues, albeit in small amounts. However, other antigens still appear to exist almost entirely in or on tumour cells so that the antigens of human tumours may be subdivided into either tumour-associated macromolecules or tumour-specific antigens. The elucidation of the chemical nature of the tumour-specific antigens may result in important advances in cancer diagnosis and therapy. As many are organ specific, it should be possible to evolve test systems which will enable tumours to be diagnosed and located before they become apparent clinically. On the other hand the tumour-associated macromolecules, of which the oncofetal antigens are the principal examples, are found in elevated amounts in some non-neoplastic disorders. It is now clear that serial estimation of the levels of these macromolecules is of considerably more diagnostic value than single random measurements. Current work is establishing their value in the detection of recurrent and metastatic tumours before they become apparent by other methods, which is probably their most important role, and also their value as aids to monitor therapeutic efficacy. The future use of both types of antigen may unfold a new era in cancer detection and therapy but many basic chemical and immunological studies are needed before their clinical use can be fully defined.

Our studies have confirmed that raised plasma levels of carcinoembryonic antigen (C.E.A.) occur with many but not all malignant tumours, particularly those of the gastrointestinal tract, breast, and bronchus. However, the incidence of raised values may reach 30% in diseases associated with inflammation or regeneration or both. Consequently, it cannot serve yet as a routine screening test for cancer. Effective surgical therapy results in high plasma C.E.A. levels returning to normal. Subsequent rises appear to develop with tumour recurrence or spread. At present the most useful role for C.E.A. seems to be in monitoring patients during the post-therapeutic followup period. Further basic work is required before C.E.A. can become of routine medical value.