Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Köcher, Thomas; Zheng, Min; Bolli, Martin; Simon, Ronald; Förster, T.; Schultz‐Thater, Elke; Remmel, Eugenia; Noppen, Christoph; Schmid, U; Ackermann, Daniel; Mihatsch, Michael J.; Gasser, Thomas C.; Heberer, Michael; Sauter, Guido; Spagnoli, Giulio C.

doi:10.1002/ijc.10540

Cited by 63 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…15,23,37,42,43 There is debate regarding the association of CT antigen expression on a protein level and tumor grade. A relationship between MAGE expression and tumor grade has been shown in transitional cell carcinomas of the urinary bladder 44 and in certain types of brain tumors. 45 In our analysis, mAb 57B and CT7-33 were statistically significantly more often immunoreactive in high-grade tumors (95% of all positive cases (P ¼ 0.001) and 89% of all positive cases (P ¼ 0.0129), respectively).…”

Section: Discussionmentioning

confidence: 99%

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

et al. 2005

View full text Add to dashboard Cite

Cancer-testis (CT) antigens are expressed in a variety of malignant tumors, but in normal adult tissue, they are only expressed in testicular germ cells. Owing to this tumor-associated expression pattern, these antigens are of major interest as potential targets for immunotherapy and possibly for diagnostic purposes. This study was performed to analyze the expression of four CT antigens, NY-ESO-1, MAGE-A3, MAGE-A4, and CT7/MAGE-C1, in endometrial carcinoma using immunohistochemistry, and to correlate expression with histologic subtypes, grade, and expression of WT1 and p53. Formalin-fixed paraffin-embedded tissues of 130 endometrial carcinomas of the following types and grades were analyzed using a tissue microarray: 85 endometrioid carcinomas (FIGO grade 1, 39; grade 2, 11; and grade 3, 35), 18 papillary serous carcinomas, 12 clear cell carcinomas, 13 malignant mixed mullerian tumors, one mucinous adenocarcinoma, and one undifferentiated carcinoma. The following anti-CT monoclonal antibodies/antigens were studied by immunohistochemistry: monoclonal antibody ES121/NY-ESO-1, monoclonal antibody M3H67/MAGE-A3, monoclonal antibody 57B/ MAGE-A4, and monoclonal antibody CT7-33/CT7. The CT expression data were compared to WT1 and p53 protein expression as analyzed in a previous study. Positive staining with anti-CT monoclonal antibodies was graded as follows: focal, o5% positive cells; 1 þ , 5-25% cells; 2 þ , 26-50% cells; 3 þ , 51-75%; and 4 þ , 475% cells. The 3 þ and 4 þ staining patterns were considered homogeneous patterns of potential clinical significance and were scored positive for statistical analysis. In low-grade tumors, the most immunoreactivity was seen with mAb M3H67 but little labeling was observed with the other monoclonal antibodies. In high-grade tumors, monoclonal antibodies M3H67 (25%), 57B (23%), and CT7-33 (20%) showed the highest reactivity, while ES121 showed the lowest immunoreactivity (6%). The staining pattern was mostly heterogeneous. Statistical significance was found solely for the correlation of monoclonal antibody 57B staining and p53 expression. No correlation was found for any anti-CT monoclonal antibody staining and clinical stage or for anti-CT staining and WT1 expression. CT antigens CT7, MAGE-A3 and MAGE-A4, but not NY-ESO-1, are expressed in high-grade endometrial carcinomas, and expression of MAGE-A4 is correlated with the presence of overexpressed p53.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Similar results were also shown in NY-ESO-1 expression in melanoma 28 and MAGE-A4 in transitional cell carcinoma. 29 Second, the IHC staining pattern is heterogeneous in different HCC samples, the expression of the FATE/BJ-HCC-2 antigen in tumor cells ranging from focal to a large mass of tumor cells. This heterogeneity appears to be a consistent morphologic characteristic of all CT antigens in many tumor types.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

Yang

Dong

Qiao

et al. 2005

Laboratory Investigation

View full text Add to dashboard Cite

FATE/BJ-HCC-2 is a newly identified cancer/testis (CT) antigen, which was detected in tumor tissues and testis. As previous studies of FATE/BJ-HCC-2 expression pattern were mainly based on messenger RNA (mRNA) analysis, it is necessary to investigate its actual protein expression pattern in tumor tissues for the evaluation of its application value. In this study, we produced specific polyclonal antibody (pAb) to the recombinant FATE/ BJ-HCC-2 protein and analyzed the FATE/BJ-HCC-2 antigen expression in normal and malignant tissues by the immunohistochemical approach. The results showed that there was no detectable FATE/BJ-HCC-2 antigen expressed in normal tissues except testis. In hepatocellular carcinoma (HCC) tissues, the FATE/BJ-HCC-2 antigen was detected in 20% (7/35) specimens. All samples that expressed the FATE/BJ-HCC-2 antigen were of poorly or moderately differentiated HCC. The stained antigen was located in the cytoplasm and the staining pattern showed heterogeneity from focal to more than 40% of the tumor cells. The FATE/BJ-HCC-2 antigen was also expressed in other tumor tissues. The results of [ 3 H]thymidine incorporation showed that FATE/BJ-HCC-2 protein enhanced tumor cell proliferation after transfection of FATE/BJ-HCC-2 gene in HCC cell line (Po0.01). This effect could be specifically blocked by anti-FATE/BJ-HCC-2 pAb. Serological screening showed that the antibody specific to the FATE/BJ-HCC-2 antigen was detected in 7.7% (4/52) patients. Notably, the four positive patients bore poorly or moderately differentiated HCC. FATE/BJ-HCC-2 mRNA transcript was detected in the peripheral blood mononuclear cells (PBMCs) of 46.67% patients whose resected HCC tissue samples were positive for FATE/BJ-HCC-2 mRNA, which implicated tumor cell dissemination in blood circulation and may relate to the metastasis of HCC. Thus, FATE/BJ-HCC-2 may be a valuable candidate CT antigen for polyvalent vaccines in tumor immunotherapy and an assisting diagnostic marker for prognosis of the disease.

show abstract

“…Samples were scored as positive if a staining of weak intensity was detectable in >66% of tumor cells or of moderate intensity in >34% of tumor cells or of strong intensity in any percentage of tumor cells. 11,12 Statistical analysis Ninety-five percent confidence intervals were computed for the frequencies of total C/T antigen positivity. The percentages of tumors expressing NY-ESO-1/LAGE-1 and MAGE-A C/T anti- Aminoacid sequences of different C/T antigens were aligned together with random peptide sequences from E coli clones adhering to MAb coated plates (n ¼ 5 for D8.38, panel A and n ¼ 7 for 57B, panel B).…”

Section: Immunohistochemistrymentioning

confidence: 99%

NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

Bolli

Schultz‐Thater

Zajac

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The characterization of the expression pattern of different families of cancer/testis (C/T) antigens in different tumors, at the protein level, might be of relevance in the development of multiantigen vaccine preparations for active specific immunotherapy. We have used tissue microarray (TMA) technology to explore in large numbers of tumor specimens the expression of NY-ESO-1/LAGE-1 C/T antigens and its correlation with MAGE-A expression by using D8.38 and 57B monoclonal antibodies (MAb). The epitopes recognized by these reagents in C/T antigens were identified by molecular mapping by using a bacterial expression system. Out of 2,052 samples, 119 (5.8%) scored positive upon staining with D8.38 NY-ESO-1/LAGE-1-specific MAb. Expression in >10% of cases was detectable in melanoma and basalioma (31.6 and 18.2%, respectively), large cell carcinomas and adenocarcinomas of the lung (17.8 and 10.5%, respectively), stomach adenocarcinomas of the intestinal type (13.2%), pT2-4 bladder TCC (18.2%), nonseminomatous carcinomas of the testis (10.4%) and liposarcomas (15.4%). Simultaneous expression of NY-ESO-1/LAGE-1 and MAGE-A C/T antigens was then addressed in a TMA where 101/845 and 73/845 samples (12 and 8.6%, respectively) showed evidence of MAGE-A or NY-ESO-1/LAGE-1 specific staining, respectively. In 35/845 specimens (4.1%) concomitant expression of MAGE-A and NY-ESO-1/LAGE-1 was observed ( p = 0.0002). Discrepancies in the expression of NY-ESO-1/LAGE-1 and MAGE-A were conspicuously detectable in squamous cell carcinomas of the skin (MAGE-A positive but NY-ESO-1/LAGE-1 negative) and in liposarcomas (NY-ESO-1/LAGE-1 positive, but MAGE-A negative). Taken together, these data suggest novel areas of application of C/T antigens targeted active specific immunotherapy possibly based on multiantigen vaccine preparations. ' 2005 Wiley-Liss, Inc.Key words: cancer/testis antigens; NY-ESO-1/Lage-1; MAGE-A; epitope mapping Cancer/testis (C/T) antigens are a group of proteins characterized by a peculiar expression profile, mostly limited to male germinal cells and cancer cells of diverse histological origin. 1 Among C/T antigens, NY-ESO-1 appears to play an important role since it is probably the most immunogenic member of the group and it is also capable to induce humoral responses in addition to specific cytotoxic T lymphocytes (CTL) and CD4þ T cells. 2,3 Remarkably, most recently a highly homologous determinant, LAGE-1, has been reported to be able to induce specific regulatory CD25þ/CD4þ in melanoma tumor infiltrating lymphocytes (TIL). 4 Immunohistochemical detection of NY-ESO-1 has been made possible by the generation of monoclonal antibodies (MAb) capable of recognizing the target protein in paraffin embedded tissues, as reported by us and others. 5,6 However, the fine specificity of these reagents at the molecular level was not clarified, the number of tissues tested was relatively limited and the issue of the coexpression together with other C/T antigen families was not addressed. Here, we mapped epitopes recognized by rea...

show abstract

Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Cited by 63 publications

References 28 publications

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

Contact Info

Product

Resources

About