Preoperative Diagnosis of Lynch Syndrome With DNA Mismatch Repair Immunohistochemistry on a Diagnostic Biopsy

• DOI: 10.1097/dcr.0b013e318231db1f
• Publication Date: 2011-11-08T09:45:08Z
• Authors: S. K. Warrier; A. H. Trainer; A. C. Lynch; C. Mitchell; R. Hiscock; S. Sawyer; A. Boussioutas; A. G. Heriot
• Keywords: Adenosine Triphosphatases; Adult; Colon; Biopsy; Nuclear Proteins; Middle Aged; 16. Peace & justice; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; Immunohistochemistry; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; DNA Repair Enzymes; MutS Homolog 2 Protein; 0302 clinical medicine; Case-Control Studies; Biomarkers, Tumor; Humans; MutL Protein Homolog 1; Germ-Line Mutation; Adaptor Proteins, Signal Transducing; Aged; Mismatch Repair Endonuclease PMS2

DNA mismatch repair immunohistochemistry on tumor tissue is a simple, readily available, and cost-effective method of identifying patients with Lynch syndrome in the postoperative setting. The aim of the study was to assess whether the mismatch repair status of a colorectal cancer can be confirmed by mismatch repair immunohistochemistry on preoperative biopsy.Germline positive patients with Lynch syndrome were identified from a prospectively collected Familial Cancer Clinic database. Preoperative colorectal cancer biopsy specimens were obtained from the source pathology provider to generate a cohort of matched preoperative and postoperative specimens. The specimens were sectioned and stained for 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2). An age-matched cohort to compare specimens was selected from Bethesda positive but mismatch repair immunohistochemistry negative patients. All slides were reviewed by a single blinded pathologist. The Wilson method was used to calculate a true underlying proportion of patients for whom the preoperative result matched the postoperative test result with a 95% confidence interval.Of 128 germline positive mutation carriers, 40 patients (mean age 41, SD 11.3) had colorectal resections. Thirty-three preoperative specimens were retrievable and were matched with biopsies from 33 controls. The germline mutations included in the study were 8 MLH1, 19 MSH2, 3 MSH6, and 2 PMS2. In patients where germline positive status was known, sensitivity was 100% (95% CI 89.2-100) and specificity was 100% (95% CI 89.2-100). Identical sensitivity and specificity were observed in 33 age-matched patients. The sensitivity of the endoscopic biopsy in predicting germline status was 94.9% (95% CI 80.4-98.3).The mismatch repair disease status of a colorectal cancer can be reliably confirmed by mismatch repair immunohistochemistry on a diagnostic colorectal cancer biopsy sample before definitive surgery. Ascertaining a diagnosis of Lynch syndrome before definitive surgery can influence surgical planning.