Sessile serrated adenomas of the large bowel. Clinicopathologic and immunohistochemical study including comparison with common hyperplastic polyps and adenomas.

Sikl's Department of Pathology, Medical Faculty Hospital, Charles University, Pilsen, Czech Republic.
Ceskoslovenska patologie 08/2006; 42(3):133-8.
Source: PubMed


Sessile serrated adenoma (SSA) is a newly characterized type of the large bowel adenoma. It arises in hyperplastic polyp (HP) and represents a precursor lesion of colorectal carcinoma with microsatellite instability. SSAs differ from common HPs by abnormal proliferation of the crypt epithelium and by nuclear atypia. We examined 15 SSAs from 15 patients. The age range was 25-80 years (average 60 years). Six patients were females and 9 were males. For comparison, we examined 10 conventional tubular adenomas and 10 common HPs with vesicular cells. The sites of SSAs were as follows: 8 in rectum, 4 in rectosigmoid colon, 1 in transverse colon, 1 next to mucinous carcinoma of ascending colon, 1 in anastomosis after resection of the transverse colon adenocarcinoma. The diameter of the lesions ranged from 5 to 12 mm. Histologically, SSAs showed asymmetrical proliferation of the epithelium, irregular shape of the crypts with their branching and some crypt dilatations especially in the basal parts of the crypts. Cellular atypia (dysplasia) was usually low. In 5 cases the nuclei were focally stratified and localized in the lower part of the cells. High-grade dysplasia was found only in SSA adjacent to mucinous adenocarcinoma. Immunohistochemically, SSAs showed secretion of gastrointestinal mucin expressing MUC2 and MUC5A. Both MUC2 and MUC5A were also positive in mucinous carcinoma. In previous studies these expressions were considered specific for serrated type of carcinogenesis. However, our study found positivity of MUC2 and MUC5A also in conventional adenomas. Expression of p53 in SSAs was minimal. SSAs have malignant potential comparable with conventional adenomas and for this reason they must be distinguished from HPs.

Download full-text


Available from: Michal Zamecnik
  • Source
    • "Hyperplastic polyps seem to be linked to colon cancer via the recently reclassified (sessile) serrated adenoma, previously classified as a hyperplastic polyp [11]. A serrated adenoma arises within a hyperplastic polyp but differs from an ordinary hyperplastic polyp by abnormal proliferation of crypt epithelium and by nuclear atypia [12]. In one study, approximately 18% of removed polyp specimens originally classified as hyperplastic were reclassified as serrated adenomas using the revised classification [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Colon cancer is believed to arise from two types of precursor polyps via two distinct pathways: conventional adenomas by the conventional adenoma-to-carcinoma sequence and serrated adenomas according to the serrated adenoma-to-carcinoma theory. Conventional adenomas arise from mutation of the APC gene; progression to colon cancer is a multistep process. The fundamental genetic defect in serrated adenomas is unknown. Environmental factors can increase the risk for colon cancer. Advanced colon cancer often presents with symptoms, but early colon cancer and premalignant adenomatous polyps commonly are asymptomatic, rendering them difficult to detect and providing the rationale for mass screening of adults over age 50.
    Preview · Article · Apr 2008 · Gastroenterology Clinics of North America
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colon cancer is the most common nondermatologic cancer in Italy and throughout Europe, with about 250,000 cases annually in Europe, about half of whom die. Yet, colon cancer is largely preventable through intensive, mass screening programs to remove premalignant colonic polyps. The persistently high incidence and mortality is largely due to ineffective implementation of established screening protocols due to patient fears about screening tests, physician under-referral for screening, and test costs. Colon cancer mostly arises from adenomas, recognized as colonic polyps, but may occasionally arise from the sessile serrated adenoma. Adenomatous polyposis coli (APC) gene mutation is the key molecular step in adenoma formation. Mismatch repair gene mutation is a less common alternative pathway. Progression from adenomas to colon cancer is a multistep process, involving mutations of the DCC, k-ras, and p53 genes; loss of heterozygosity in which cells loose one allele of some genes from chromosomal loss; and DNA methylation which can silence DNA expression. Numerous environmental factors can increase the risk of colon cancer, presumably by modulating these molecular pathways. While colon cancer in an advanced and incurable stage often produces clinical findings, premalignant adenomatous polyps and early, highly curable, colon cancer are often asymptomatic. This phenomenon renders adenomas or early cancers difficult to detect by clinical presentation and provides the rationale for mass screening of asymptomatic adults over 50 years old for early detection and prevention of colon cancer. Colonoscopy is the primary screening test. All polyps identified at colonoscopy are removed by colonoscopic polypectomy. Endoscopic mucosal resection is required for deeply penetrating noncancerous polyps. Colonoscopy is repeated every ten years if the index colonoscopy revealed no lesions, but is repeated more frequently if adenomatous polyps were identified at this colonoscopy due to an increased risk of subsequent polyps or colon cancer. Flexible sigmoidoscopy every few years with annual fecal occult blood testing is a significantly less sensitive screening protocol. Virtual colonoscopy is controversial as a screening test due to widely variable reported RESULTS: Computerized tomography is standardly used to preoperatively detect distant colon cancer metastases, while endosonography is being increasingly used for locoregional staging of rectal cancer. Stool genetic markers and videocapsule endoscopy are promising, but currently experimental, screening tests.
    No preview · Article · Jan 2008 · Minerva gastroenterologica e dietologica
  • [Show abstract] [Hide abstract]
    ABSTRACT: We obtained 22 sessile serrated adenomas (SSAs) and 19 hyperplastic polyps (HPs) and performed immunolabeling for cytokeratins (CKs) 7 and 20, CDX2, beta-catenin, and p53 to determine the role of these markers in aiding distinction of lesions with neoplastic potential. Patients with SSAs more frequently had a prior or coexistent tubular adenoma (P = .004) that was right-sided (P = .00001) and larger (P = .03). No difference in CK7, CK20, or p53 labeling was found after correction for colonic location. However, CDX2 labeling was significantly lower in SSAs (P = .02) and was predominantly confined to the crypt bases, whereas it was diffusely positive in HPs (P < .001). Surprisingly, aberrant nuclear labeling for beta-catenin was found in 9 (41%) of the SSAs but in none of the HPs (P < .002). We propose that beta-catenin and/or CDX2 immunolabeling may have diagnostic usefulness in the evaluation of serrated polyps. These findings also suggest that Wnt signaling has a role in SSA development.
    No preview · Article · Apr 2008 · American Journal of Clinical Pathology
Show more