Molecular characteristics of poorly differentiated adenocarcinoma and signet‐ring‐cell carcinoma of colorectum

• Published in: International journal of cancer Vol. 84; no. 1; pp. 33 - 38
• Main Authors: Kawabata, Yuichi, Tomita, Naohiro, Monden, Takushi, Ohue, Masayuki, Ohnishi, Tadashi, Sasaki, Masaya, Sekimoto, Mitsugu, Sakita, Isao, Tamaki, Yasuhiro, Takahashi, Juro, Yagyu, Toshio, Mishima, Hideyuki, Kikkawa, Nobuteru, Monden, Morito
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 19.02.1999; Wiley-Liss
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; bcl-2-Associated X Protein; Biological and medical sciences; Carcinoma, Signet Ring Cell - genetics; Carcinoma, Signet Ring Cell - pathology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Replication - genetics; Female; Frameshift Mutation; Gastroenterology. Liver. Pancreas. Abdomen; Genes, ras; Humans; Male; Medical sciences; Microsatellite Repeats - genetics; Middle Aged; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Receptors, Transforming Growth Factor beta - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Suppressor Protein p53 - genetics; Tumors; Adenocarcinoma; Histological grading; Human; Rectal disease; Transforming growth factor β; Cytokine; Malignant tumor; Carcinogenesis; Colonic disease; Pathology; Signet ring cell carcinoma; Histopathology; C-Onc gene; Rectum; Digestive diseases; Genetics; Intestinal disease; Colon; Mutation; Protooncogene; Biological receptor
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990219)84:1<33::AID-IJC7>3.0.CO;2-Z

In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet‐ring‐cell carcinomas (sig) of the colorectum, K‐ras gene mutation, p53 immunostaining and microsatellite instability (MSI) were analyzed for a comparison with 46 cases of colorectal carcinomas of the well or moderately differentiated type (well/mod). In addition, the mutations of simple repeated sequences in the transforming‐growth‐factor‐β type‐II receptor (T β R‐II) gene and the BAX gene were analyzed as possible targets for DNA replication errors. Mutation of the K‐ras gene in the por, sig and well/mod specimens was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift mutation of the T β R‐II gene was detected in 27.5% of the por and none of the sig specimens, while corresponding figures for mutation of the BAX gene were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K‐ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumor's location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T β R‐II or the BAX gene was found. These results suggest that poorly differentiated and signet‐ring‐cell carcinomas have a genetic background different from that of well or moderately differentiated carcinomas of the colorectum, and that DNA‐replication error is at least partly involved in the carcinogenesis of these specific types of colorectal carcinomas. Int. J. Cancer (Pred. Oncol.) 84:33–38, 1999. © 1999 Wiley‐Liss, Inc.