PURPOSE: The aim of this study was to identify prognostic subgroups of microsatellite instability-high (MSI-H) colorectal cancers by combined analysis of 10 well-established immunohistochemical tumor markers and 7 clinicopathologic features. EXPERIMENTAL DESIGN: Using a tissue microarray, immunohistochemistry was done on 223 cases of MSI-H cancers for the following protein markers: raf-1 kinase inhibitor protein, receptor for hyaluronic acid-mediated motility, apoptosis protease activating factor-1, mammalian sterile20-like kinase 1, p21, p27, p53, ephrin B2 receptor, Ki-67, and epidermal growth factor receptor. Seven clinicopathologic features and all tumor markers were evaluated in univariate and multivariable analyses. RESULTS: RHAMM overexpression [P < 0.001; hazard ratio [HR; 95% confidence interval (95% CI)], 3.86 (2.19-6.81)], loss of p21 [P = 0.002; 0.33 (0.16-0.67)], and higher N stage [P < 0.001; 3.31 (1.9-5.8)] were independent adverse prognostic factors. RHAMM/p21 combinations were evaluated by N stage. Significant differences in survival were observed with various RHAMM/p21 combinations (P < 0.001). Both node-negative and node-positive patients with RHAMM- tumors survived more than 120 months. Node-positive RHAMM+ patients had a strikingly worse prognosis [16.0 (10.0-63.0) months] and could further be divided into p21- patients [14.0 (9.0-27.0) months] and p21+ patients surviving 47.0 months. RHAMM+/p21- node-negative patients had a significantly shorter survival time than RHAMM+/p21+ tumors (P = 0.021). CONCLUSION: These results suggest that the combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in MSI-H colorectal cancer. Based on the prognostic subgroups identified in our cohort, node-negative patients overexpressing RHAMM but with loss of p21 may derive a potential benefit from postoperative treatment, whereas adjuvant chemotherapy should be reconsidered for MSI-H node-positive RHAMM- tumors.
PURPOSE: The aim of this study was to identify prognostic subgroups of microsatellite instability-high (MSI-H) colorectal cancers by combined analysis of 10 well-established immunohistochemical tumor markers and 7 clinicopathologic features. EXPERIMENTAL DESIGN: Using a tissue microarray, immunohistochemistry was done on 223 cases of MSI-H cancers for the following protein markers: raf-1 kinase inhibitor protein, receptor for hyaluronic acid-mediated motility, apoptosis protease activating factor-1, mammalian sterile20-like kinase 1, p21, p27, p53, ephrin B2 receptor, Ki-67, and epidermal growth factor receptor. Seven clinicopathologic features and all tumor markers were evaluated in univariate and multivariable analyses. RESULTS:RHAMM overexpression [P < 0.001; hazard ratio [HR; 95% confidence interval (95% CI)], 3.86 (2.19-6.81)], loss of p21 [P = 0.002; 0.33 (0.16-0.67)], and higher N stage [P < 0.001; 3.31 (1.9-5.8)] were independent adverse prognostic factors. RHAMM/p21 combinations were evaluated by N stage. Significant differences in survival were observed with various RHAMM/p21 combinations (P < 0.001). Both node-negative and node-positive patients with RHAMM- tumors survived more than 120 months. Node-positive RHAMM+ patients had a strikingly worse prognosis [16.0 (10.0-63.0) months] and could further be divided into p21- patients [14.0 (9.0-27.0) months] and p21+ patients surviving 47.0 months. RHAMM+/p21- node-negative patients had a significantly shorter survival time than RHAMM+/p21+ tumors (P = 0.021). CONCLUSION: These results suggest that the combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in MSI-H colorectal cancer. Based on the prognostic subgroups identified in our cohort, node-negative patients overexpressing RHAMM but with loss of p21 may derive a potential benefit from postoperative treatment, whereas adjuvant chemotherapy should be reconsidered for MSI-H node-positive RHAMM- tumors.
Authors: Brian P Teng; Melissa D Heffler; Eric C Lai; Ya-Li Zhao; Charles M LeVea; Vita M Golubovskaya; Kelli M Bullarddunn Journal: Anticancer Agents Med Chem Date: 2011-09 Impact factor: 2.505
Authors: Shuji Ogino; Katsuhiko Nosho; Natsumi Irahara; Jeffrey A Meyerhardt; Yoshifumi Baba; Kaori Shima; Jonathan N Glickman; Cristina R Ferrone; Mari Mino-Kenudson; Noriko Tanaka; Glenn Dranoff; Edward L Giovannucci; Charles S Fuchs Journal: Clin Cancer Res Date: 2009-10-13 Impact factor: 12.531
Authors: Shuji Ogino; Kaori Shima; Katsuhiko Nosho; Natsumi Irahara; Yoshifumi Baba; Brian M Wolpin; Edward L Giovannucci; Jeffrey A Meyerhardt; Charles S Fuchs Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-06 Impact factor: 4.254
Authors: Shuji Ogino; Katsuhiko Nosho; Natsumi Irahara; Shoko Kure; Kaori Shima; Yoshifumi Baba; Saori Toyoda; Li Chen; Edward L Giovannucci; Jeffrey A Meyerhardt; Charles S Fuchs Journal: Clin Cancer Res Date: 2009-06-23 Impact factor: 12.531