Tumor‐specific antigens in cutaneous T‐cell lymphoma: Expression and sero‐reactivity

Eichmüller, Stefan B.; Usener, Dirk; Thiel, Daniela; Schadendorf, Dirk

doi:10.1002/ijc.10967

Cited by 41 publications

(34 citation statements)

References 53 publications

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“…The difference may be attributed to several factors, including ethnic and molecular differences. Most of the cases (7/8, 95 %) presented with Ann Arbor stage IV and 6/8 are HIV negative which are associated with poor prognosis [21,26].…”

Section: Cytogenetic Analysismentioning

confidence: 99%

“…Though the reason for this observation is not clear, it may be due, in part, to the over-representation of HIV infection in men compared to women in developed countries [23]. Another contributing factor could be the fact that a number of cancer-related genes, known as cancer/testis antigens (CTAs) that are located on the X-chromosome (MAGEA1, SSX1, SSX4, and CTAG1/2) [24][25][26], are highly upregulated in PBL, which mainly affect male individuals [27]. However, CTAs can be aberrantly expressed in different types of cancer [28,29].…”

Section: Cytogenetic Analysismentioning

confidence: 99%

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Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

et al. 2015

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Background: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin's lymphoma. Characterized by its aggressive nature and plasmacytic differentiation, PBL remains a therapeutic and diagnostic challenge; it generally has a poor prognosis with very few long-term survivors and most patients dying within 2 years from initial presentation. PBL has been reported in several other countries; however, there have been no reported cases from Saudi Arabia. Here, we report 8 cases of PBL depicting the clinical presentation, immunocompetency, immunphenotypic characterization, diagnostic challenges and treatment outcome. Methods: The medical records were reviewed for clinical presentation, staging, laboratory data, radiological studies, treatments, and outcomes. A broad immunohistochemical panel consisting of CD45, CD3, CD20, CD79a, Pax5, CD38, CD138, MUM1, EMA, Kappa, Lambda, CD 56, CD30, Bcl-2, Bcl-6, Alk-1, Ki-67, EBV-LMP-1, and HHV8 was performed. Results: The tumors predominantly exhibited immunoblastic/plasmablastic or plasmacytic morphologic features and had a plasma cell-like immunophenotype. All cases were immunoreactive for CD38, CD138 and MUM1 confirming plasma cell differentiation of the tumor cells. CD20 was negative for all cases; whereas CD79a and Pax5 were weakly positive in 2cases. All 8 cases were EBV-LMP-1/EBER-1 negative, and 1 case was HHV8 positive. Similar to previously published studies, PBL in Saudi Arabia is characterized by male predominance (6/8), median age 51.5 years (mean age 46 years), associated with early dissemination, poor response to therapy, and limited survival (average survival time, 6.4 months, median overall survival 5.5 months). However, it does have some unique features. It occurs more commonly in immunocompetent persons (6/8, 75 %), is not associated with EBV infection (0/8), and nodal involvement (either primary or secondary) is common among patients (6/8). In addition, extra-oral sites are more common than oral/nasal cavities (7/8) and the c-myc gene is not common (1/8, 12.5 %).

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Section: Cytogenetic Analysismentioning

confidence: 99%

Section: Cytogenetic Analysismentioning

confidence: 99%

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

et al. 2015

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“…Interestingly, expression of several CT antigens, including GAGE, can be induced by the hypomethylating agent 5-aza-2 0 -deoxycytidine (Sigalotti et al, 2002), and it has been shown that induction of transcription correlates with hypomethylation of CT antigen promoters (Janssen et al, 1999;De Smet et al, 2004). There also seem to be individual differences in the regulation of the transcription of GAGE genes since the GAGE members are not always co-expressed (Kobayashi et al, 2000;Eichmuller et al, 2002;Eichmuller et al, 2003).…”

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confidence: 99%

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

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“…[14][15][16][17][18][19][20] NY-ESO-1 21,22 has been isolated in esophageal carcinoma but has also been found in several other malignancies, such as melanoma; neuroblastoma; carcinoma of the ovary, breast, and lung; and in synovial sarcoma. [23][24][25][26][27][28][29] The CT7 antigen was identified by the SEREX approach using a melanoma cell line SK-MEL37 and allogeneic sera from a melanoma patient. 30 CT7 is identical to MAGE-C1, identified independently by another group using representational difference analysis.…”

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confidence: 99%

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

et al. 2005

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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.

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Tumor‐specific antigens in cutaneous T‐cell lymphoma: Expression and sero‐reactivity

Cited by 41 publications

References 53 publications

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

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

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