Clinicopathologic and Genetic Characterization of Traditional Serrated Polyps of the Colon.
Baojin Fu, Shinichi Yachida, Richard Morgan, Yi Zhong, Elizabeth A Montgomery, Christine A Iacobuzio-Donahue. The Johns Hopkins Hospital, Baltimore, MD
Background: Traditional serrated adenomas (TSAs) are a type of colorectal polyp with neoplastic potential that are morphologically distinct from sessile serrated adenomas. The clinicopathologic and genetic features of TSAs are uncertain as prior studies have often combined these two entities.
Design: Routinely processed polypectomy specimens and associated clinicopathologic data from 24 patients with TSA were collected. TSA morphology was confirmed for each polyp based on the presence of serrated epithelium, ectopic crypt formations (ECF), cytoplasmic eosinophilia and pencillate nuclei. Unstained sections were immunolabeled for beta-catenin, p53, Ki67 and activated caspase-3. DNA was extracted from paraffin sections and used for PCR amplification and bidirectional sequencing of the KRAS and BRAF oncogenes.
Results: Among all 24 patients, 16 (67%) were male and 23 (96%) were Caucasian. The mean age was 61.8 yrs (range 40-86). Twenty-one (88%) of TSAs were located in the left colon. The mean size of all TSAs was 0.9 cm (range 0.1 to 2.5 cm). Conventional epithelial dysplasia in a TSA, seen as foci of increased nuclear/cytoplasmic ratio, nuclear crowding and loss of differentiation was present in 15/24 (63%) TSAs; none showed high-grade dysplasia. Abnormal nuclear accumulation of beta-catenin was identified in 7/24 (29%) TSAs, and abnormal nuclear accumulation of p53 in 2/24 (8%) TSAs. Abnormal Ki-67 labeling (defined as labeling of surface epithelium) was observed in 12/24 (50%) TSAs. By contrast, activated caspase-3 labeling was either negative or labeled only rare cells in all TSAs. Sequencing identified activating KRAS mutations in 11 TSAs (46%) and activating BRAF mutations in 9 TSAs (38%). KRAS and BRAF mutations were mutually exclusive and in total accounted for 20/24 (83%) TSAs. There was no difference in the clinicopathologic features of KRAS mutant versus BRAF mutant TSAs. However, nuclear labeling of beta-catenin was more common in TSAs with BRAF mutations (5/9, 56%) versus those with a KRAS mutation (1/11, 9.1%) (P=0.05).
Conclusions: Colorectal polyps with morphologic features of TSA are represented by two genetic variants. Wnt pathway activation in TSA predominantly occurs in the setting of BRAF activation. Abnormalities in Wnt signaling and p53 are more common in larger TSAs associated with conventional epithelial dysplasia, suggesting these lesions undergo a genetic progression as described for other colorectal polyps.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 87, Monday Morning