Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours.
OBJECTIVE
To correlate the expression of a series of apoptotic and oncogene markers (including p53, Bcl-2, BAX, Bcl-XL, p21WAF,1/CIP1, cyclin D1, HER-2/neu) in thymic epithelial tumours with histological type, stage and resectability and to determine whether the information on HER-2/neu would be valuable in identifying patients who are eligible for anti-HER-2/neu treatment.


RESULTS
Immunohistochemical stains were performed on 16 cases of non-neoplastic thymus, 63 thymomas and 17 thymic carcinomas. Fluorescence in-situ hybridization (FISH) for HER2 was performed to validate the gene amplification. Eighteen thymomas were positive for p53 and 14 of them were low-expressors, with positive cells below 10%. All thymic carcinomas revealed over-expression of p53 with positive cells either between 10% and 50% or >50%. The expression of p53 correlated with histological type and stage in thymoma. In both thymoma and thymic carcinoma, there was a statistically significant correlation between p53 status and resectability, with low expressors having a higher likelihood of being resectable. Thymic carcinomas, regardless of the histological subtypes, uniformly expressed Bcl-2, while thymomas showed no or only weak cytoplasmic immunoreactivity. Most thymomas and thymic carcinomas were negative for Bcl-XL, p21WAF,1/CIP1 and cyclin D1. The expression of BAX was inconsistent among different histological types. Nine thymic carcinomas revealed membranous positivity for HER-2/neu, but no HER2 gene amplification could be demonstrated by FISH in any of the cases.


CONCLUSIONS
p53 and Bcl-2 are more implicated in the development of thymic carcinoma than thymoma. The higher level of p53 expression and the strong immunopositive pattern of Bcl-2 in thymic carcinomas have potential value in the differential diagnosis and prediction of aggressiveness and resectability. On account of the absence of HER2 amplification, patients would probably not benefit from anti-HER-2/neu treatment.
Pan
C-C
CC
Department of Pathology, National Yang-Ming University, and Veterans General Hospital-Taipei, Taiwan. ccpan@vghtpe.gov.tw
Chen
P C-H
PC
Wang
L-S
LS
Lee
J-Y
JY
Chiang
H
H
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013945:Thymoma / Q000378:metabolism* / Q000473:pathology; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53