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, Hubert Fenton, Marc R. Lewin, Ashlie L. Burkart, Christine A. Iacobuzio-Donahue, Wendy L. Frankel, Elizabeth Montgomery

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)564-571
Number of pages8
JournalAmerican journal of clinical pathology
Volume126
Issue number4
DOIs
StatePublished - Oct 2006

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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