A "field change" of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma.
BACKGROUND
Colorectal cancer is associated with a "field change" of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death.


OBJECTIVE
To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa.


METHODS
PATIENTS undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus).


METHODS
Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts.


RESULTS
85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3-43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0-36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0-0.0%).


CONCLUSIONS
The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.
Badvie
S
S
Department of Surgery, Chelsea & Westminster Hospital, London, UK. sara.badvie@doctors.org.uk
Hanna-Morris
A
A
Andreyev
H J N
HJ
Cohen
P
P
Saini
S
S
Allen-Mersh
T G
TG