Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium.
The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death, that involves an intrinsic normal cell death program. Bcl-2 overexpression was originally described in a follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. Variation in the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium, is known to occur as a result of hormonal changes in both physiological and pathological circumstances. In this study we examined bcl-2 protein expression in a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14 secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen and progesterone receptors status, with the proliferative activity and with clinicopathological features. The expression of bcl-2 protein was lower in the group of carcinomas, when compared with the cases of adenomatous hyperplasia (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07). In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p = 0.026) and in secretory endometrium it was correlated with ER status (p = 0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated with increased tumor grade (p = 0.04). A positive relationship between bcl-2 expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001, respectively), was also found. These results indicate that bcl-2 expression may play a role in the inhibition of apoptosis in endometrial carcinoma and its expression seems to be associated with tumor differentiation and cell proliferation.
Department of Forensic Pathology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Antigony
A
Mitselou
Elli
E
Ioachim
Evagelia
E
Kitsou
Theodore
T
Vougiouklakis
Nektaria
N
Zagorianakou
Georgios
G
Makrydimas
Stella
S
Stefanaki
Niki J
NJ
Agnantis
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D004714:Endometrial Hyperplasia / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005656:Fungal Proteins; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D005656:Fungal Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid; D012697:Serine Endopeptidases; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins