Ichiro Ohki

A Study of the Rate of Superficial Cancer Progressing to Advanced Cancer of the Colon and Rectum

Abstract: In order to clarify the rate of superficial cancer developing into colorectal cancer histologically, we examined horizontal growth type cancer in the residual mucosa of 68 samples with submucosal (sm) cancer, 91 with cancer with invasion of the muscularis propria (mp) and 311 with invasion deeper than the subserosa (ss). Among 68 samples of sm cancer, residual mucosa persisted in 65 (95.6%) and horizontal growth type cancer was found in 17 (26.2%). There was no significant difference in size between the horizontal and non‐horizontal growth type cancers. Among 91 samples of mp cancer, residual mucosa persisted in 15 (15.5%), horizontal growth type cancer was found in five (33.3%), and the latter were significantly smaller than non‐horizontal growth type cancers (p< 0.05). Among 311 samples of ss cancer, residual mucosa persisted in 12 (3.9%) and horizontal growth was found in six (50.0%). In cancer with invasion deeper than the ss layer, malignant tissue is generally lost from the mucosa, such that the rates may not reflect the actual incidence. The rates of progression from superficial to sm cancer (26.2%) and mp cancer (33.3%) may be close to the present rate of superficial cancer developing into colorectal cancer. We conclude that the rate of superficial cancer developing into invasive cancer is at least 26.2%, and that superficial type cancers have a strong tendency to invade the mp even when smaller than protruded type cancers. It may be useful to focus on horizontal growth type cancers to elucidate the growth and development of colorectal cancer.

K-ras Codon 12 Mutation and Horizontal Growth of Colorectal Cancer

Abstract: K‐ras codon 12 mutations and horizontal growth were examined in 121 colorectal cancers to clarify genetic contributions to tumorigenesis. Invasion was submucosal [SMCa] in 61 cases and to the muscularis propria [PMCa] in 60. Growth patterns were further classified into polypoid [PG] and nonpolypoid [NPG] types. Horizontal growth cancers were defined as lesions associated with horizontally aligned cancerous glands. The K‐ras codon 12 mutation frequency was higher in PG SMCa than in NPG SMCa (49% versus 0%, respectively), and in PG PMCa compared to NPG PMCa (60% versus 24%, respectively). The K‐ras codon 12 mutation was less frequent in horizontal growth SMCa than in nonhorizontal growth SMCa (0% versus 49%, respectively), and in horizontal growth PMCa compared to nonhorizontal growth PMCa (0% versus 64%, respectively). The frequency of horizontal growth was higher in NPG SMCa than in PG SMCa (100% versus 0%, respectively), and in NPG PMCa compared to PG PMCa (76% versus O%, respectively). The frequencies of NPG carcinoma with horizontal growth and with wild type K‐ras in SMCa were both 26%. NPG carcinoma with horizontal growth and with wild type K‐ras in PMCa both occurred at a frequency of 22%. Our results suggest that NPG type carcinomas with horizontal growth do not result from K‐ras codon 12 mutations, and may arise through very different genetic pathways and histologic processes. At least 22% of early colorectal cancers may progress to advanced cancer of superficial origin. (Dig Endosc 1999; 11: 125–131)

A case of CA19‐9‐producing adenocarcinoma of the remnant stomach resembling gastritis cystica polyposa

Gastritis cystica polyposa (GCP) is a well‐known precancerous lesion of the remnant stomach. We report a case of carbohydrate antigen (CA) 19–9‐producing well‐differentiated adenocarcinoma of the remnant stomach that resembled GCP. The patient was a 66‐year‐old Japanese man who had undergone subtotal gastrectomy 20 years previously. The tumor developed in the remnant stomach at the anastomotic line. Histologically, the lesion completely encircled the gastroenterostomy stoma. There was florid growth of glands with cystic dilatation and minimal atypia extending through the thickened muscularis propria into the subserosa. Small foci of less well‐differentiated adenocarcinoma were also detected, including irregular glands or small clusters of mucus‐producing cells with moderate atypia. Immunostaining revealed that numerous tumor cells were positive for carcinoembryonic antigen and CA19‐9, whereas only a few cells were positive for p53. The macroscopic, histopathological and immunohistochemical findings indicated a diagnosis of CA19‐9‐producing well‐differentiated adenocarcinoma of the remnant stomach. To avoid underdiagnosis, careful attention should be paid to the above‐mentioned morphological features and immunohistochemical findings, in addition to the endoscopic findings.

p53 Overexpression and K-ras Codon 12 Mutations in Submucosal Invasive Colorectal Cancer

We examined histological findings, p53 overexpression and K‐ras codon 12 mutations and the histology of submucosal invasive (sm) colorectal cancers. Sixty specimens of sporadic sm cancer were obtained by surgical resection or endoscopic polypectomy. p53 expression was examined by im‐munohistochemical staining using the streptavidin‐biotin method. K‐ras codon 12 mutations were detected by polymerase chain reaction (PCR) and dot blot hybridization. These tumors were classified as horizontal or nonhorizontal growth sm cancers. Fifteen of 60 (25%) superficial type horizontal growth cancers gave rise to sm cancers. There was no significant difference in size between horizontal and nonhorizontal growth sm cancers. There was no significant difference in the frequency of p53 expression between horizontal [8/15 (53.3%)] and nonhorizontal [22/45 (48.9%)] growth sm cancers. The frequency of K‐ras codon 12 point mutations was significantly lower in horizontal growth [0/15 (0%)] sm cancers as compared to nonhorizontal growth [22/45 (48.9%)] sm cancers. We conclude that the development of superficial type horizontal growth cancers may involve a distinct genetic pathway.

Immunohistochemical Study of Colorectal Polyps with Antibodies against CEA, CA19‐9, CA125, CA15‐3 (DF3), PCNA and p53

Abstract: We analyzed the expression of CEA, CA19‐9, CA125, CA15‐3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19‐9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15‐3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19‐9, CA15‐3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19‐9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15‐3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15‐3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15‐3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas.