Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes

J Gastroenterol. 2002;37(5):354-62. doi: 10.1007/s005350200049.


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.

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, p53 / genetics
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness