Overexpression of p53, Mutation of hMLH1 and Microsatellite Instability in Gastric Carcinomas: Clinicopathologic Implications and Prognosis

Purpose: Mutated p53 is a tumor suppressor gene, hMLH1 is a mismatch repair gene, and hypermethylation of hMLH1 follows microsatellite instability (MSI). This research`s aim is to investigate mutated p53, inactivated hMLH1 and MSI in gastric cancer and their clinicopathologic implications. Methods: Between 2003 and 2007, 618 patients underwent curative radical gastrectomy for gastric cancer at Seoul National University Bundang Hospital in Korea. We reviewed their medical charts and the pathologic reports with immunohistochemistry for p53, hMLH1 and polymerase chain reaction for MSI in 509, 499, and 561 cases, respectively. These genetic markers were statistically compared with clinicopathologic features and postoperative survival. Results: The expression ratios of mutated p53, inactivated hMLH1, and MSI were 32.8%, 8.4%, and 8.7%, respectively. Mutation of p53 occurred more frequently in aged group (over 40), differentiated group (against the non-differentiated group), intestinal type, infiltrative type and positive lymph node metastasis group. Inactivated hMLH1 occurred more frequently in aged group, differentiated group, intestinal type and expanding growth type group. MSI was found more frequently in aged group, intestinal type and expanding growth type group. All three genetic markers had no significant associations with the 5-year survival. Conclusion: We identified significant relationships between mutated p53, inactivated hMLH1, and MSI with some clinicopathologic features of gastric cancer. However, there were no apparent relationships between p53, hMLH1, and MSI and prognosis.KU KB, 2007, J KOREAN SURG SOC, V72, P283WOERNER SM, 2006, CANCER BIOMARK, V2, P69LIU P, 2005, WORLD J GASTROENTERO, V11, P4904Lee HS, 2002, MODERN PATHOL, V15, P632Nakajima T, 2001, INT J CANCER, V94, P208Samowitz WS, 2001, AM J PATHOL, V158, P1517Rugge M, 2000, J CLIN PATHOL-MOL PA, V53, P207Wu MS, 2000, GENE CHROMOSOME CANC, V27, P403OH SH, 2000, J KOREAN SURG SOC, V59, P206Fleisher AS, 1999, CANCER RES, V59, P1090Leung SY, 1999, CANCER RES, V59, P159Monig SP, 1997, DIGEST DIS SCI, V42, P2463Thibodeau SN, 1996, CANCER RES, V56, P4836Starzynska T, 1996, CANCER, V77, P2005DosSantos NR, 1996, GASTROENTEROLOGY, V110, P38Peddanna N, 1995, ANTICANCER RES, V15, P2055TAMURA G, 1995, CANCER RES, V55, P1933SERUCA R, 1995, INT J CANCER, V64, P32CORREA P, 1994, CANCER RES, V54, pS1941BODMER W, 1994, NAT GENET, V6, P217RHYU MG, 1994, ONCOGENE, V9, P29UCHINO S, 1993, INT J CANCER, V54, P759TAHARA E, 1993, J CANCER RES CLIN, V119, P265CORREA P, 1992, CANCER RES, V52, P6735MARTIN HM, 1992, INT J CANCER, V50, P859HOLLSTEIN MC, 1991, CANCER RES, V51, P4102YONISHROUACH E, 1991, NATURE, V352, P345HARRIS AL, 1990, J PATHOL, V162, P5