[Significance of cancer cell growth and apoptosis in morphogenesis of colorectal cancer].
The present study was carried out to elucidate the relationship between cancer cell growth and apoptosis in morphogenesis of colorectal cancer, and the role of p53 expression, one of apoptosis-related genes, in apoptosis. Specimens from 82 cases of colorectal cancer, all surgically resected, were divided into intramucosal polypoid growth (PG) and nonpolypoid growth (NPG) types according to Shimoda's classification. Expressions of proliferating cell nuclear antigen (PCNA) and p53 protein were assessed by immunohistochemical staining, and apoptosis by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Immunohistological detection of p53 protein was performed by the use of Pab1801. In the assessment of PCNA and apoptosis the numbers of positive cells per 1000 tumor cells were expressed as PCNA labeling index (L.I.) and apoptosis labeling index (Apo L.I.), respectively. In tumor invading muscularis propria (mp), the cancer tumor tissue was equally divided into three by the depth, top, middle, and bottom, and the number of apoptosis-positive cells per 500 tumor cells was calculated per each depth of invasion and compared between PG and NPG types. PCNA L.I. was 658.5 +/- 127.1 (mean +/- SD) in PG type. When determined according to depth of invasion, PCNA L.I. was 533.8 +/- 188.2 for tumor invading submucosa (sm), 741.8 +/- 62.2 for mp, and 679.2 +/- 94.3 for tumor invading subserosa or penetrating the serosa (ss-a). The corresponding values in the NPG type were 651.9 +/- 176.2, 482.2 +/- 227.1, 766.2 +/- 90.7, and 690.9 +/- 84.3, respectively. There was no significant difference in the relationship of PCNA L.I. with the depth of invasion in both growth types. Apo L.I. was 19.9 +/- 9.8 in PG type. When determined according to depth of invasion, Apo L.I. was 29.2 +/- 9.7 for sm, 21.7 +/- 9.0 for mp, and 15.4 +/- 7.0 for ss-a. The corresponding values in the NPG type were 52.8 +/- 25.1, 67.5 +/- 25.6, 37.2 +/- 9.4, and 52.6 +/- 26.3, respectively. Apo L.I. of NPG type was significantly higher than that of PG type in each depth of invasion (p < 0.01). In mp tumor the numbers of apoptosis-positive cells in the top, middle, and bottom of the PG type were 8.0 +/- 4.8, 11.8 +/- 3.9, and 12.9 +/- 5.9, and the corresponding values of the NPG type were 26.6 +/- 7.6, 17.3 +/- 5.3, and 11.8 +/- 4.3, respectively. The number of apoptosis in the top and middle of the lesion of NPG tumors was significantly higher than that of PG tumors. There was no difference in the number of apoptosis in the bottom of the lesion between the NPG and the PG types. There was no significant difference in the Apo L.I. between p53 positive cancers and negative cancers. These results indicate that colorectal cancers show a pattern of PG if apoptosis is low, and a pattern of NPG if apoptosis is high, and that apoptosis of colorectal cancer cell is not regulated by p53.
Seki
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First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D017209:Apoptosis; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007417:Intestinal Polyps / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53