Pathological and genetic correlates of apoptosis in the progression of colorectal neoplasia.
OBJECTIVE
Apoptosis is commonly observed in a variety of human tumors, and some of the genetic events which control this process have been identified in vitro. The aim of this study was to determine the frequency of apoptosis in colorectal neoplasms and to examine its relationship to a number of pathological parameters, to the presence of mutations in the p53 tumor suppressor gene, and to overexpression of the bcl-2 oncoprotein.


METHODS
A total of 109 colorectal neoplasms (26 adenomas 83 carcinomas) were examined. An in situ end-labelling assay was used to detect apoptosis in paraffin-embedded tumor sections, and scores were determined by light microscopy. The p53 and bcl-2 status were determined by immunohistochemistry.


RESULTS
Apoptotic frequency increased with tumor progression. Normal mucosa contained significantly fewer apoptotic cells than adenomas or carcinomas. Similarly adenomas showed less apoptosis than carcinomas, and the frequency of apoptosis increased with Dukes' stage. Overall, changes in apoptotic frequency were inversely related to the level of bcl-2 expression, but were not related to the p53 status of the tumors.


CONCLUSIONS
The frequency of apoptosis in colorectal neoplasia appears to increase in the course of tumor progression in association with a decline in bcl-2 expression, but is not influenced by p53 gene mutations.
Hawkins
N
N
School of Pathology, University of New South Wales, Australia. N.Hawkins@unsw.edu.au
Lees
J
J
Hargrave
R
R
O'Connor
T
T
Meagher
A
A
Ward
R
R
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004249:DNA Damage; D053938:DNA Fragmentation; D018450:Disease Progression; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53