title: Colorectal Tumors From Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency.
abstract: Microsatellite instability (MSI) in colorectal cancer cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations such as in patients with Lynch syndrome. Universal screening initiatives for Lynch syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations.
  
  
  
  We performed a retrospective analysis of 253 surgically resected, primary colorectal adenocarcinoma specimens identified from the University of Miami tumor registry from 2005 through 2010. We collected clinical data, including overall survival (OS), the proportion of patients alive at specific intervals, from non-Hispanic white, Hispanic, and black patients matched by stage. We performed immunohistochemical staining to detect MMR proteins in all specimens and polymerase chain reaction analysis of 51 tumors to detect MSI.
  
  
  
  We detected MMR deficiency in 28 of 253 cases (11.1%), evenly distributed among blacks (9.6%), non-Hispanic whites (10.4%), and Hispanics (12.6%) (P = .79). Combined deficiencies in MLH1 and PMS2 were found in 23 of 28 MMR-deficient samples (82.1%); MSH2 and MSH6 were most frequently absent in tumor samples from Hispanics (P = .03). Eleven of 51 tumor samples (21.6%) had high levels of MSI, and we observed a high level of concordance between MMR and MSI (κ = .81). OS was significantly better in patients whose tumors had deficient MMR (hazard ratio for patients with MMR-deficient tumors vs MMR proteins intact = 0.37; 95% confidence interval, 0.15-0.91; P = .03). Race and ethnicity were not significant predictors of OS.
  
  
  
  MMR deficiency in colorectal tumors occurs with similar rates among patients of different racial and ethnic groups, which is based on immunohistochemical analysis of 253 primary tumor specimens. This finding indicates the potential value of universal testing of colorectal cancer by immunohistochemistry in minority populations and confirms the benefit of MMR deficiency to OS.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Shivali
authors.initials: S
authors.lastname: Berera
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Tulay
authors.initials: T
authors.lastname: Koru-Sengul
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Feng
authors.initials: F
authors.lastname: Miao
authors.affiliation: Division of General Internal Medicine, Department of Internal Medicine, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Olveen
authors.initials: O
authors.lastname: Carrasquillo
authors.affiliation: Department of Pathology, University of Miami Leonard Miller School of Medicine, Miami, Florida.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nadji
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky/Sylvester Comprehensive Cancer Center, Lexington, Kentucky.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hosein
authors.affiliation: Center for Genome Technology, John P. Hussman Institute for Human Genomics, University of Miami Leonard Miller School of Medicine, Miami, Florida.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: McCauley
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Miami Leonard Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida. Electronic address: dsussman@med.miami.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sussman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D001932:Brain Neoplasms / Q000150:complications* / Q000453:epidemiology*; D015179:Colorectal Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D045643:DNA Repair Enzymes / Q000032:analysis; D005006:Ethnicity; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000150:complications* / Q000453:epidemiology*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D045643:DNA Repair Enzymes
keywords: Colorectal Cancer; DNA Mismatch Repair; Lynch Syndrome; Medically Underserved Populations; Microsatellite Instability; Minority