PURPOSE: Although most stage II colon cancers are potentially curable by surgery alone, approximately 20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer. EXPERIMENTAL DESIGN: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined. RESULTS: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2(low) plus TUCAN(low) were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1(low) plus TUCAN(high)) survived compared with 83% of others at 5 years after diagnosis (P< 0.0001). CONCLUSIONS: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.
PURPOSE: Although most stage II colon cancers are potentially curable by surgery alone, approximately 20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer. EXPERIMENTAL DESIGN: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined. RESULTS: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2(low) plus TUCAN(low) were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1(low) plus TUCAN(high)) survived compared with 83% of others at 5 years after diagnosis (P< 0.0001). CONCLUSIONS: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.
Authors: Anne Benard; Eliane C M Zeestraten; Inès J Goossens-Beumer; Hein Putter; Cornelis J H van de Velde; Dave S B Hoon; Peter J K Kuppen Journal: Apoptosis Date: 2014-11 Impact factor: 4.677
Authors: Ji Hye Yim; Won Gu Kim; Min Ji Jeon; Ji Min Han; Tae Yong Kim; Jong Ho Yoon; Suck Joon Hong; Dong Eun Song; Gyungyub Gong; Young Kee Shong; Won Bae Kim Journal: Thyroid Date: 2013-12-13 Impact factor: 6.568
Authors: Michael J O'Connell; Ian Lavery; Greg Yothers; Soonmyung Paik; Kim M Clark-Langone; Margarita Lopatin; Drew Watson; Frederick L Baehner; Steven Shak; Joffre Baker; J Wayne Cowens; Norman Wolmark Journal: J Clin Oncol Date: 2010-08-02 Impact factor: 44.544
Authors: Venkat R Katkoori; Catalina Suarez-Cuervo; Chandrakumar Shanmugam; Nirag C Jhala; Tom Callens; Ludwine Messiaen; James Posey; Harvey L Bumpers; Sreelatha Meleth; William E Grizzle; Upender Manne Journal: J Gastrointest Oncol Date: 2010-12
Authors: Maryla Krajewska; Layton H Smith; Juan Rong; Xianshu Huang; Marc L Hyer; Nikolajs Zeps; Barry Iacopetta; Steven P Linke; Allen H Olson; John C Reed; Stan Krajewski Journal: J Histochem Cytochem Date: 2009-03-16 Impact factor: 2.479