Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes.
BACKGROUND
Many colorectal carcinomas are known to develop from preexisting polypoid adenomas; however, they can also develop from so-called "flat adenomas". To elucidate the growth patterns of flat- or depressed-derived colorectal carcinomas, we investigated the clinicopathologic characteristics and genetic changes of invasive carcinomas.


METHODS
Seventy-five colorectal carcinomas were classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG) type, and 7 lateral growth (LG) type. All of them had histologically infiltrated the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by polymerase chain reaction-single-strand conformation polymorphism analysis, and overexpression of p53 protein was analyzed by immunohistochemistry.


RESULTS
No DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors existing in the right colon was significantly higher in LG carcinomas (71%) than in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was significantly higher in the UG carcinomas than in the DG and LG carcinomas (52% vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of 7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG (57%), and DG (50%) carcinomas.


CONCLUSIONS
These results suggest that UG carcinomas develop on the basis of the adenoma-carcinoma sequence, while the development of DG and LG carcinomas is different from that of UG carcinomas.
Kurahashi
Toshinori
T
Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Kaneko
Kazuhiro
K
Makino
Reiko
R
Mitamura
Keiji
K
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness