Cell cycle regulators and apoptosis-associated proteins in relation to proliferative activity and degree of apoptosis in HNPCC versus sporadic endometrial carcinoma.
OBJECTIVE
Mismatch repair gene malfunction occurs early in the carcinogenesis of hereditary non-polyposis colorectal cancers (HNPCCs), leading to an accelerated accumulation of mutations and possibly to change in expression of cell cycle proteins. There is strong evidence that tumorigenesis in HNPCCs differs from sporadic ones. HNPCC-related endometrial cancers are less well studied. Our aim was to compare expression of cell cycle and apoptosis-related proteins in relation to proliferation and apoptosis in HNPCC-related and sporadic endometrial cancers to identify differences in their carcinogenetic pathways.


RESULTS
Eighteen HNPCC-related endometrial cancers, each matched by tumour type, stage and grade with two sporadic endometrial cancers, were examined for proliferation, apoptosis and the expression of oestrogen and progesterone receptors, cyclin B1, D3 and E, p21, p27, bcl-2, bax, p53 and COX-2. No differences in proliferation or apoptotic indices were detected between HNPCC-related and sporadic endometrial cancers. Cyclin B1 expression was significantly higher in HNPCC-related cancers than in sporadic endometrial cancers. More HNPCC-related endometrial cancers had total loss of bax expression.


CONCLUSIONS
Apart from differences in cyclin B1 and bax expression, HNPCC-related and sporadic endometrial cancers are comparable. The subtle differences detected are consistent with the minor clinical diversity between HNPCC-related and sporadic endometrial cancers.
Rijcken
F
F
Department of Gynaecology, University Medical Centre Groningen, Groningen, the Netherlands. fleurrijcken@hotmail.com
van der Zee
A
A
van der Sluis
T
T
Boersma-van Ek
W
W
Kleibeuker
J
J
Hollema
H
H
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics; D049109:Cell Proliferation; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D019926:Cyclin B / Q000032:analysis / Q000235:genetics; D056744:Cyclin B1; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D051028:bcl-2-Associated X Protein