Mark Bettington1,2,3, Neal Walker2,3, Christophe Rosty2,3,4, Ian Brown3,5, Andrew Clouston2,3,5, Diane McKeone1, Sally-Ann Pearson1, Kerenaftali Klein6, Barbara Leggett1,2,7, Vicki Whitehall1,2,8. 1. The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. 2. School of Medicine, The University of Queensland, Brisbane, QLD, Australia. 3. Envoi Specialist Pathologists, Brisbane, QLD, Australia. 4. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Carlton, Vic., Australia. 5. Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia. 6. Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. 7. The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. 8. Department of Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
Abstract
AIMS: Most colorectal polyps are classified readily, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture causes diagnostic confusion. We aimed to (i) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features. METHODS AND RESULTS: We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild-type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, cytosine-phosphate-guanosine (CpG) island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers [MutL homologue 1 (MLH1), p16, p53, β-catenin, Ki67, CK7 and CK20]. We found that serrated TVAs can be diagnosed reliably, and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β-catenin. CONCLUSIONS: The serrated TVA can be diagnosed reliably and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma.
AIMS: Most colorectal polyps are classified readily, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture causes diagnostic confusion. We aimed to (i) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features. METHODS AND RESULTS: We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild-type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, cytosine-phosphate-guanosine (CpG) island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers [MutL homologue 1 (MLH1), p16, p53, β-catenin, Ki67, CK7 and CK20]. We found that serrated TVAs can be diagnosed reliably, and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β-catenin. CONCLUSIONS: The serrated TVA can be diagnosed reliably and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma.
Authors: Tilman T Rau; Raja Atreya; Daniela Aust; Gustavo Baretton; Matthias Eck; Katharina Erlenbach-Wünsch; Arndt Hartmann; Alessandro Lugli; Robert Stöhr; Michael Vieth; Anna M Wirsing; Inti Zlobec; Tiemo Katzenberger Journal: J Pathol Clin Res Date: 2016-02-25