A Histology-Based Model for Predicting Microsatellite... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

A Histology-Based Model for Predicting Microsatellite Instability in Colorectal Cancers

Hyde, Angela BSc*; Fontaine, Daniel MD†; Stuckless, Susan MSc‡; Green, Roger PhD*; Pollett, Aaron MD§; Simms, Michelle MSc*; Sipahimalani, Payal MSc*; Parfrey, Patrick MD‡; Younghusband, Banfield PhD*

*Discipline of Genetics, Memorial University of Newfoundland

‡Clinical Epidemiology Unit, Memorial University of Newfoundland

†Department of Pathology, Eastern Health, St John's, Newfoundland, Canada

§Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Grant Support/Funding: The Canadian Institute of Health Research Interdisciplinary Team Award on Colorectal Cancer at Memorial University and University of Toronto (2001 to 2011). Walter and Jessie Boyd & Charles Scriver MD/PhD Studentship Award (A.H.) (Canadian Institute of Health Research Institute of Genetics and the Canadian Gene Cure Foundation).

The authors have no conflicts of interest to disclose.

Correspondence: Banfield Younghusband, PhD, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6 (e-mail: [email protected]).

Abstract

Identifying colorectal cancers (CRCs) with high levels of microsatellite instability (MSI-H) is clinically important. MSI-H is a positive prognostic marker for CRC, a predictive marker for resistance to standard 5-fluorouracil-based adjuvant chemotherapy, and an important feature for identifying individuals and families with Lynch syndrome. Our aim was to compare and improve upon the existing predictive pathology models for MSI-H CRCs. We tested 2 existing models used to predict MSI-H tumors, (1) Revised Bethesda Guidelines and (2) MsPath, in our population-based cohort of CRCs diagnosed less than 75 years from Newfoundland (N=710). We also scored additional histologic features not described in the other models. From this analysis, we developed a model for the prediction of MSI-H CRCs; Pathologic Role in Determination of Instability in Colorectal Tumors (PREDICT). An independent pathologist validated this model in a second cohort of all CRCs (N=276). Tumor histology was a better predictor of MSI status than was personal and family history of cancer. MsPath identified MSI-H CRCs with a sensitivity of 92.1% and a specificity of 37.8%, whereas the Revised Bethesda Guidelines had a sensitivity of 81.3% and a specificity of 39.5%. PREDICT included some new histology features, including peritumoral lymphocytic reaction and increased proportion of plasma cells in the tumor stroma. PREDICT was superior to both existing models in the development cohort with a sensitivity of 97.4% and a specificity of 53.9%. In the validation cohort, sensitivity was 96.9% and specificity 76.6%. We conclude that PREDICT is a good predictor of MSI-H CRC.