Microsatellite instability and hMLH1 and hMSH2 gene expression in Taiwanese hereditary nonpolyposis colorectal cancer
Journal
Journal of the Formosan Medical Association
Journal Volume
103
Journal Issue
5
Pages
331-336
Date Issued
2004
Author(s)
Abstract
Background and Purpose: The mutation rate of hMHS2 and hMLH1 (20%) in Taiwanese hereditary nonpolyposis colorectal cancer (HNPCC) is lower than that reported in other countries. This study aimed to examine the microsatellite instability (MSI) status and gene expression pattern of Taiwanese HNPCC in an effort to establish correlation between these data and results of prior genetic screening. Methods: The "Bethesda markers" were used for the MSI analysis. Tumor and neighboring tissues were obtained from 10-mm sections of neutral formalin-fixed, paraffin-embedded, hematoxylin and eosin-stained specimens with a PixCell laser-capture microdissector. Four-mm sections were used for the immunohistochemical analysis by avidin-biotin complex method and final coloring with diaminobenzidine. A pathologist performed scoring of the pathological specimens twice, using a double-blinded methodology. Thirteen tissue blocks from 8 HNPCC families (Amsterdam's criteria) were included in this study. Results: Althought the majority of the HNPCC tissues dislayed a MSI-high phenotype (10/13, 76.9%), lack of expression of MSH2 and MLH1 was infrequent. Furthermore , only 1 germ-line mutation was detected in the peripheral blood leukocytes of the patients whose tumors had lost protein expression of MSH2 or MLH1. Conclusions: Our results indicate that the pathogenesis of Taiwanese HNPCC is different from that in other countries. Rather than immunohistochemical analysis, MSI status, and genetic screening, clinical history remains a reliable method for diagnosis of HNPCC in Taiwanese the population.
SDGs
Other Subjects
avidin; biotin; diaminobenzidine; eosin; formaldehyde; hematoxylin; microsatellite DNA; paraffin; protein MLH1; protein MSH2; carrier protein; DNA; DNA binding protein; microsatellite DNA; MLH1 protein, human; MSH2 protein, human; nuclear protein; oncoprotein; protein MSH2; tumor protein; adult; aged; article; cancer tissue; carcinogenesis; clinical article; colorectal cancer; controlled study; correlation coefficient; diagnostic accuracy; diagnostic value; DNA determination; family history; female; gene expression; gene frequency; gene mutation; genetic marker; genetic screening; germ line; histopathology; human; human tissue; immunohistochemistry; laser capture microdissection; leukocyte; male; microsatellite instability; pathologist; phenotype; population research; protein expression; reliability; scoring system; sensitivity and specificity; Taiwan; tissue fixation; colorectal tumor; DNA repair; double blind procedure; genetics; methodology; middle aged; Adult; Aged; Carrier Proteins; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Repair; DNA, Neoplasm; DNA-Binding Proteins; Double-Blind Method; Female; Genetic Markers; Genetic Screening; Humans; Immunohistochemistry; Male; Microsatellite Repeats; Middle Aged; MutS Homolog 2 Protein; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins; Sensitivity and Specificity; Taiwan
Type
journal article