Low Ki-67 Proliferation Index Is an Indicator of Poor Prognosis in Gastric Cancer

Background and Objectives: We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Methods: Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. Results: Low Ki-67 PI was correlated with poorly differentiated histology (P = 0.034), an advanced T stage (P < 0.001), and lymph node metastasis (P = 0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P = 0.003, log-rank test). Multivariate analysis revealed that Ki-67 PI remained as an independent prognostic factor (hazard ratio (95% CI) = 0.670 (0.450-0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P = 0.025). Conclusions: These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. J. Surg. Oncol. 2010;102:201-206. (C) 2010 Wiley-Liss, Inc.Kim MA, 2009, HISTOPATHOLOGY, V54, P442, DOI 10.1111/j.1365-2559.2009.03247.xHejna M, 2006, ONCOLOGIST, V11, P136Novotny AR, 2006, ANN SURG, V243, P74, DOI 10.1097/01.sla.0000194088.81126.85Colozza M, 2005, ANN ONCOL, V16, P1723, DOI 10.1093/annonc/mdi352Gao CF, 2005, P NATL ACAD SCI USA, V102, P10528, DOI 10.1073/pnas.0504367102Hartgrink HH, 2005, J SURG ONCOL, V90, P153, DOI 10.1002/jso.20222ROBBINS SL, 2005, ROBBINS COTRAN PATHO, P319Garrity MM, 2004, J CLIN ONCOL, V22, P1572, DOI 10.1200/JCO.2004.10.042Pan WS, 2003, J SURG ONCOL, V82, P104, DOI 10.1002/jso.10204Allegra CJ, 2003, J CLIN ONCOL, V21, P241, DOI 10.1200/JCO.2003.05.044Ewton DZ, 2002, INT J CANCER, V98, P665, DOI 10.1002/ijc.10229PARKIN DM, 2002, CA CANC J CLIN, V55, P74Liu XP, 2001, CANCER LETT, V170, P183Lee HS, 2001, CANCER, V92, P1427Goishi H, 2000, ONCOL REP, V7, P713Scholzen T, 2000, J CELL PHYSIOL, V182, P311FENOGLIOPREISER C, 2000, WHO CLASSIFICATION T, P37Bai XZ, 1999, INT J ONCOL, V14, P785Palmqvist R, 1999, BRIT J CANCER, V79, P577Keshgegian AA, 1998, AM J CLIN PATHOL, V110, P443de Manzoni G, 1998, JPN J CLIN ONCOL, V28, P534Setala L, 1998, J CANCER RES CLIN, V124, P497Kikuyama S, 1998, ONCOL REP, V5, P867Iacopetta B, 1998, CLIN CANCER RES, V4, P1597Borre M, 1998, J UROLOGY, V159, P1609Schipper DL, 1998, EUR J CANCER, V34, P781Uzoaru I, 1998, J SURG ONCOL, V67, P33Victorzon M, 1997, ANTICANCER RES, V17, P2923Ramires M, 1997, J PATHOL, V182, P62Aaltomaa S, 1997, EUR UROL, V32, P410Kanai T, 1997, EUR SURG RES, V29, P35Muller W, 1996, BRIT J CANCER, V74, P759Takano Y, 1996, J CANCER RES CLIN, V122, P166LEWIN KJ, 1996, ATLAS TUMOR PATHOL, P245MCLOUGHLIN J, 1993, BRIT J UROL, V72, P92CATTORETTI G, 1992, J PATHOL, V168, P357WEIKEL W, 1991, BREAST CANCER RES TR, V18, P149SADI MV, 1991, CANCER, V67, P3065