Growth Patterns and Genetic Changes of Colorectal Carcinoma

Abstract

Background: Recent Japanese studies have shown that histogenesis of small colorectal carcinomas can be divided into two groups: polypoid growth arising from polypoid neoplasia, and non polypoid growth arising from flat or depressed neoplasia. This classification should be verified with genetic as well as morphologic characteristics. Subjects and Methods: In order to classify our subject into polypoid growth and non polypoid growth types both histologically and endoscopically, we selected 42 colorectal carcinomas <2 em in size (35 submucosal and seven more advanced). C,linicppathological findings, presence or absence of Ki-ras gene mutation and overexpression of p53 protein were compared between the two types. Results: Histologically, the cases were divided into 27 of the polypoid growth type and 15 of the nonpolypoid growth type. None of the non polypoid growth cases contained adenomatous remnant, whereas this was found in 75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the nonpolypoid growth cases, although it appeared in 440/0 of the polypoid growth cases. Regarding the overexpression of p53 protein, no significant difference was observed between the two types. The histological and the colonoscopic polypoid growth-nonpolypoid growth classifications correlated well with each other(agreement rate 98%), except for one lesion, which was classified as polypoid growth type endoscopically but as nonpolypoid growth type histologically. Conclusions: The histologically defined polypoid growth-nonpolypoid growth classificationmayindicate a difference inpathway of colorectal carcinogenesis. Also, colonoscopic polypoid growth-nonpolypoid growth classification is available for preoperative estimation of the genetic characteristics of small carcinomas.Key words: carcinogenesis -nonpolypoid growm -Ki-ras mutation -overexpression ofp53protein -endoscopy INTRODUCTIONRecently, Vogelstein and his co-workers (l,2) reported an interesting scenario of genetic alterations involving colorectal carcinogenesis, suggesting that Ki-ras mutation occurs early in tumorigenesis, while p53 mutation occurs later. However, this work was based on the adenoma-carcinoma sequence theory Received July 9, 1997; accepted November 18, 1997 For reprints and all correspondence: Takahiro Fujii, Department of Medicine, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277, Japan Abbreviations: PG, polypoid growth; NPG, nonpolypoid growth; EMR, endoscopic mucosal resection; FAP, familial adenomatous polyposis; HNPCC, hereditary nonpolyposis colorectal cancer; SM-C, submucosal carcinoma; Adv-C, advanced carcinoma; PCR-SSCP, polymerase chain reaction single-strand conformation polymorphism obtained from polypoid adenomas to invasive carcinoma, and may not be applicable to flat or depressed tumors (3,4). Yamagata et al. (5) reported that flat adenomas manifested a lower incidence of the Ki-ras codon 12 mutation than did polypoid adenomas, and suggested that the above difference may indicate that the colorect...

Clinicopathological Characteristics of Small Advanced Colorectal Carcinoma

“…In the present study, we investigated the clinicopathological characteristics of small advanced carcinomas ≤ 2 cm in diameter ; in our previous study we focused on the progression of at and depressed lesions. We previously suggested that the progression of NPG carcinomas occurs via a different pathogenetic pathway from that of PG carcinomas 7,8,22,23 . Apart from differences in macroscopic ndings, we also demonstrated that genetic alterations of NPG carcinomas were different from those of PG carcinomas, even at an advanced stage 7 .…”

“…1, 2 . Details of the assessment procedure have been described previously 8 . Brie y, formalin-xed surgical specimens were cut into blocks 5 mm in thickness and embedded in paraf n for sectioning.…”

Pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth

“…Classification criteria for PG and NPG Some minute nonpolypoid intramucosal neoplasias have been reported to transform to nonpolypoid invasive cancers (Minamoto et al, 1994;Matsumoto et al, 1995;Fujiya and Maruyama, 1997). In our previous study, almost all of NPG carcinomas infiltrating the submucosa were macroscopically flat and depressed carcinomas (Kaneko et al, 1998). We thought that PG and NPG carcinomas infiltrating the submucosa would progress PG and NPG carcinomas infiltrating beyond the submucosa.…”

“…Histologically, the resected tumour was a moderately differentiated adenocarcinoma infiltrating through the muscularis propria ( Figure 1C) with metastases to regional lymph nodes (stage III, T3N1M0). This carcinoma was classified as having a nonpolypoid growth (NPG) pattern according to our previously published criteria (Kaneko et al, 1998). While no frameshift mutation of the APC gene and no Ki-ras mutation were present, a p53 mutation was found in exon 7 (codon 244; base change, GGC to GAC; amino-acid change, Gly to Tyr).…”

“…Depending on appearance, the carcinomas were classified as having a polypoid growth (PG) or nonpolypoid growth (NPG) pattern (Figure 2A -C). Details of this assessment have been described previously (Kaneko et al, 1998). Briefly, formalin-fixed surgical specimens were cut into blocks 5 mm in thickness and embedded in paraffin for sectioning.…”