Timothy L Fitzgerald1, Swathi Rangan2, Larry Dobbs3, Shane Starr3, George Sigounas4. 1. Division of Surgical Oncology, Department of Surgery, East Carolina University, Brody School of Medicine, Greenville, North Carolina. Electronic address: fitzgerald_timothy@hotmail.com. 2. Division of Surgical Oncology, Department of Surgery, East Carolina University, Brody School of Medicine, Greenville, North Carolina. 3. Department of Pathology, East Carolina University, Brody School of Medicine, Greenville, North Carolina. 4. Department of Oncology, East Carolina University, Brody School of Medicine, Greenville, North Carolina.
Abstract
BACKGROUND: Cancer stem cells may be associated with tumor progression and prognosis for colon cancer. We hypothesized that expression of Aldehyde dehydrogenase 1 (ALDH1) would increase with tumor progression and be associated with survival. METHODS: Tissue was obtained from resection specimens for isolation of cancer stem cells. In addition, paraffin blocks from resected colon cancers with normal colon, primary tumor, and lymph node and liver metastasis from 2000 to 2010 were identified and stained with ALDH1. RESULTS: In in vitro models (adherent and tumor spheres) ALHD1+ cells grew more efficiently than ALDH1- cells. ALDH1 expression was highest in peritumoral crypt cells (0.137 μm(2), 95% confidence interval [CI] 0.125-0.356) and normal crypts (median 0.091 μm(2), 95% CI 0.064-0.299) followed by lymph node metastasis (median 0.025 μm(2), 95% CI 0-0.131) and the primary cancers (median 0.014 μm(2), 95% CI 0.0123-0.154). Samples were divided into high and low ALDH1 expression. Survival was associated with expression in the primary tumor (9 versus 23 mo, P = 0.0016) expression but not peritumoral tissue (21 versus 20.5 mo, P = 0.32), normal colon (19 versus 27 mo, P = 0.289), or lymph node metastasis (23 versus 21 mo, P = 0.69). On univariate analysis, ALDH1 expression and grade were associated with survival but ages, number of lymph node metastasis, race, or grade were not associated. On multivariate analysis, only ALDH1 status continued to be associated with survival, odds ratio 4.4, and P = 0.011. CONCLUSIONS: ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. Expression did not increase with progression from normal colon to primary tumors and metastasis.
BACKGROUND:Cancer stem cells may be associated with tumor progression and prognosis for colon cancer. We hypothesized that expression of Aldehyde dehydrogenase 1 (ALDH1) would increase with tumor progression and be associated with survival. METHODS: Tissue was obtained from resection specimens for isolation of cancer stem cells. In addition, paraffin blocks from resected colon cancers with normal colon, primary tumor, and lymph node and liver metastasis from 2000 to 2010 were identified and stained with ALDH1. RESULTS: In in vitro models (adherent and tumor spheres) ALHD1+ cells grew more efficiently than ALDH1- cells. ALDH1 expression was highest in peritumoral crypt cells (0.137 μm(2), 95% confidence interval [CI] 0.125-0.356) and normal crypts (median 0.091 μm(2), 95% CI 0.064-0.299) followed by lymph node metastasis (median 0.025 μm(2), 95% CI 0-0.131) and the primary cancers (median 0.014 μm(2), 95% CI 0.0123-0.154). Samples were divided into high and low ALDH1 expression. Survival was associated with expression in the primary tumor (9 versus 23 mo, P = 0.0016) expression but not peritumoral tissue (21 versus 20.5 mo, P = 0.32), normal colon (19 versus 27 mo, P = 0.289), or lymph node metastasis (23 versus 21 mo, P = 0.69). On univariate analysis, ALDH1 expression and grade were associated with survival but ages, number of lymph node metastasis, race, or grade were not associated. On multivariate analysis, only ALDH1 status continued to be associated with survival, odds ratio 4.4, and P = 0.011. CONCLUSIONS:ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. Expression did not increase with progression from normal colon to primary tumors and metastasis.