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Sessile Serrated Adenomas With Low- and High-Grade Dysplasia and Early Carcinomas
An Immunohistochemical Study of Serrated Lesions “Caught in the Act”

Todd B. Sheridan MD, Hubert Fenton MD, Marc R. Lewin MD, Ashlie L. Burkart MD, Christine A. Iacobuzio-Donahue MD, PhD, Wendy L. Frankel MD, Elizabeth Montgomery MD
DOI: http://dx.doi.org/10.1309/C7JE8BVL8420V5VT 564-571 First published online: 1 October 2006

Abstract

Sessile serrated adenomas (SSAs) show serrations typical of hyperplastic polyps but display architectural differences and lack traditional dysplasia. SSAs with foci of low- (LGD) or high-grade dysplasia (HGD) or early invasive carcinoma are seldom biopsied and, thus, are not well studied. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 (mismatch repair gene products) was performed on colon biopsy specimens from 11 patients (age range, 54-87 years; 4 men and 7 women) showing SSA with LGD (n = 1), HGD (n = 5), or focal invasive carcinoma (n = 5). All 11 cases showed intact nuclear staining for MSH2 and MSH6 in the SSA component; in foci of LGD, HGD, or carcinoma; and in background normal mucosa. In contrast, there was tandem loss of MLH1 and PMS2 in zones of LGD (1/1) or HGD (3/5) and early carcinoma (2/4; with concordant loss in associated HGD) but retention in SSA areas (11/11) and normal mucosa (11/11). No patient was known to have hereditary nonpolyposis colorectal cancer/Lynch syndrome. This study offers additional strong evidence that SSA is truly a precursor to at least a subset of sporadic microsatellite-unstable colorectal cancer.

Key Words:
  • Sessile serrated adenoma
  • Dysplasia
  • Serrated pathway
  • Carcinoma
  • Colorectal cancer
  • MLH1
  • Immunohistochemistry