Apoptosis Regulation Differs Between Ulcerative Colitis–Associated and Sporadic Colonic Tumors

Abstract

To clarify kinetics in ulcerative colitis (UC)-associated lesions, cell proliferation, apoptosis, and expression of apoptosis-inhibitory proteins were studied. Ki-67 labeling and survivin and bcl-2 expression were examined immunohistochemically in 22 low-grade dysplasias (LGDs), 25 high-grade dysplasias (HGDs), and 13 adenocarcinomas associated with UC, and for comparison in 21 sporadic adenomas with LGD, 22 sporadic adenomas with HGD, and 21 invasive adenocarcinomas. Apoptosis was studied with nick-end labeling and immunohistochemical analysis of single-stranded DNA. In UC-associated LGDs, Ki-67--positive cells were more frequent in the lower than the upper half of the crypt, related to bcl-2 expression, while in sporadic adenomas such cells were more common in the upper half. No difference in apoptosis was found between UC-associated LGDs and sporadic adenomas with LGD or between UC-associated HGDs and sporadic adenomas with HGD. However, UC-associated carcinomas exhibited a lower apoptotic count than their sporadic invasive counterparts. This seemed related to higher survivin expression without a significant difference between the 2 types of invasive lesions regarding bcl-2 levels. Apoptosis is less frequent in UC-associated than in sporadic invasive colon carcinomas, this being linked to elevated survivin expression. The control of apoptosis may be different in the 2 types of tumorigenesis.

Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy

“…Two (10,12) of three studies (10 -12) related to the prognosis mentioned above demonstrated an inverse correlation between survivin expression and apoptosis (the third had no data available for apoptosis). Other studies of colorectal cancer have also revealed such an inversion relationship (7,14), although Agui et al (13) and the present study did not prove this in colonic and rectal cancers. One of the reasons for the controversial results, other than the varied numbers of patients and different tumor characteristics and methods used to detect apoptotic cells in these studies, may be "surgery-related apoptosis."…”

“…We also observed that the invasive margins of some tumors showed strong survivin expression. Furthermore, survivin expression increased in the transition from adenomas with low dysplasia to high dysplasia and to colorectal carcinoma (7,14). However, survivin expression decreased from colonic primary cancer to liver metastasis (13).…”

Immunohistochemical characteristics of duodenal adenomas in familial adenomatous polyposis with special reference to cell kinetics

“…Methodologically, TUNEL staining requires an assessment of the morphological appearance for the detection of apoptotic cells, because nick-end labeling can result in false-positive staining by detecting late apoptotic stages featuring DNA fragmentation [23]. However, such a provisional false positivity does not seem to have affected our results, because the AI in the current study was equivalent to the value shown previously in colorectal adenoma with low-grade dysplasia [23,24].…”

Disruption of the p53-p53r2 DNA repair system in ulcerative colitis contributes to colon tumorigenesis

“…With reduction of p53R2 in neoplastic lesions, the DNA repair system might not function properly. Even with multiple hits on genes regulating the cell cycle, DNA repair and apoptosis would not occur, 38 leading eventually to carcinoma development.…”