Einar F Sverrisson1, Michael S Zens2, Dennis Liang Fei3, Angeline Andrews2, Alan Schned4, David Robbins5, Karl T Kelsey6, Hua Li7, James DiRenzo8, Margaret R Karagas2, John D Seigne9. 1. Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH. 2. Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH. 3. Cancer Biology Section, National Institutes of Health, Bethesda, MD. 4. Department of Pathology (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH. 5. Molecular Oncology Program, Department of Surgery, University of Miami, Miami, FL. 6. Department of Community Health, Brown University, Providence, RI. 7. Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD. 8. Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH. 9. Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH. Electronic address: john.d.seigne@hitchcock.org.
Abstract
INTRODUCTION: Dysregulation of the hedgehog signaling pathway has been linked to the development and progression of a variety of different human tumors including cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the clinicopathological factors that are potentially related to expression of Gli1, the transcription factor that is thought to be the most reliable marker of hedgehog pathway activation in bladder cancer. METHODS: Bladder cancer cases were identified from the New Hampshire State Cancer Registry as histologically confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31, 2004. Immunohistochemical analysis was performed on a tissue microarray to detect Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs) and their 95% CIs for Gli1 positivity for pathological category using T category (from TNM), invasiveness, and grade with both the World Health Organization 1973 and World Health Organization International Society of Urological Pathology criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and recurrence for both Ta-category and invasive bladder tumors (T1+). RESULTS: A total of 194 men and 67 women, whose tumors were assessable for Gli1 staining, were included in the study. No appreciable differences in Gli1 staining were noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors were more likely to stain for Gli1 as compared with T1-category tumors (adjusted OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non-muscle-invasive bladder tumors expressing Gli1 were less likely to recur (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1 was absent. CONCLUSION: Our findings indicate that Gli1 expression may be a marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk of recurrence in this group.
INTRODUCTION: Dysregulation of the hedgehog signaling pathway has been linked to the development and progression of a variety of different humantumors including cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the clinicopathological factors that are potentially related to expression of Gli1, the transcription factor that is thought to be the most reliable marker of hedgehog pathway activation in bladder cancer. METHODS:Bladder cancer cases were identified from the New Hampshire State Cancer Registry as histologically confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31, 2004. Immunohistochemical analysis was performed on a tissue microarray to detect Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs) and their 95% CIs for Gli1 positivity for pathological category using T category (from TNM), invasiveness, and grade with both the World Health Organization 1973 and World Health Organization International Society of Urological Pathology criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and recurrence for both Ta-category and invasive bladder tumors (T1+). RESULTS: A total of 194 men and 67 women, whose tumors were assessable for Gli1 staining, were included in the study. No appreciable differences in Gli1 staining were noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors were more likely to stain for Gli1 as compared with T1-category tumors (adjusted OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non-muscle-invasive bladder tumors expressing Gli1 were less likely to recur (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1 was absent. CONCLUSION: Our findings indicate that Gli1 expression may be a marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk of recurrence in this group.
Authors: Dennis Liang Fei; Hua Li; Courtney D Kozul; Kendall E Black; Samer Singh; Julie A Gosse; James DiRenzo; Kathleen A Martin; Baolin Wang; Joshua W Hamilton; Margaret R Karagas; David J Robbins Journal: Cancer Res Date: 2010-02-23 Impact factor: 12.701
Authors: M Craig Hall; Sam S Chang; Guido Dalbagni; Raj Som Pruthi; John Derek Seigne; Eila Curlee Skinner; J Stuart Wolf; Paul F Schellhammer Journal: J Urol Date: 2007-12 Impact factor: 7.450
Authors: Hadi Danaee; Heather H Nelson; Margaret R Karagas; Alan R Schned; Tara Devi S Ashok; Tomoko Hirao; Ann E Perry; Karl T Kelsey Journal: Oncogene Date: 2002-07-25 Impact factor: 9.867