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

Sheridan, Todd; Fenton, Hubert; Lewin, Marc R.; Burkart, Ashlie L.; Iacobuzio‐Donahue, Christine A.; Frankel, Wendy L.; Montgomery, Elizabeth

doi:10.1309/c7je-8bvl-8420-v5vt

Cited by 57 publications

(97 citation statements)

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“…Although MUC6 is clearly 'morphology-associated', there is also evidence to suggest that it may be a 'pathway-associated' marker in colorectal cancer. In addition to its association with loss of MLH-1 expression in this and one other study, 9 other preliminary studies show that MUC6 is more commonly positive in microsatellite-unstable than in microsatellite-stable colon cancer 34 and that it is largely negative in 'traditional' adenomatous polyps (unpublished personal data). Thus, it is our hope that the findings will provide both a diagnostic aid to the practicing pathologist, and a window into the pathogenesis of these unique colonic polyps.…”

Section: Discussionsupporting

confidence: 70%

“…The polyps found to contain cytological dysplasia were classified as traditional serrated adenoma, 23 filiform serrated adenoma 11 or sessile serrated adenoma with dysplasia. 9 The diagnosis of traditional serrated adenoma included polyps having both serrated profile and adenomatous epithelium within the same crypts, along with characteristic eosinophilic apical cytoplasm (Figure 4a). Polyps diagnosed as filiform serrated adenoma had a similar appearance to the traditional serrated adenomas, but with characteristic elongated, filiform architecture ( Figure 4b).…”

Section: Methodsmentioning

confidence: 99%

“…For all of the cytologically dysplastic polyps, the dysplasia was graded by both pathologists as low-or highgrade based on published criteria. 9,24 A diagnosis of high-grade dysplasia required a significant degree of nuclear pleomorphism and pseudostratification, as well as architectural changes such as 'cryptwithin-crypt' formation, cribriform architecture and 'back-to-back' crypts. The presence of components morphologically consistent with sessile serrated adenoma and/or hyperplastic polyp in these polyps was also noted.…”

Section: Methodsmentioning

confidence: 99%

“…Areas of cytological dysplasia or invasive carcinoma arising in sessile serrated adenomas have been well documented in the literature. 9 Whether cytological dysplasia can also arise in a typical hyperplastic polyp has never been closely examined.…”

mentioning

confidence: 99%

“…Those polyps that have morphological features of sessile serrated adenomas described above, in combination with discrete areas of traditional adenomatous dysplasia, can be termed 'sessile serrated adenoma with dysplasia'. 9 The morphological distinction between sessile serrated adenoma and hyperplastic polyp is clinically important because of their apparently different cancer risk. Several factors affect the accurate diagnosis of sessile serrated adenomas and hyperplastic polyps.…”

mentioning

confidence: 99%

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Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

2008

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Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N ¼ 26; positive staining) from hyperplastic polyp (N ¼ 48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.

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Section: Discussionsupporting

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

2008

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Endoscopic and surgical management of serrated colonic polyps

Léonard

Dozois

Smyrk

et al. 2011

British Journal of Surgery

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The MLH1 −93 G>A promoter polymorphism and genetic and epigenetic alterations in colon cancer

Samowitz

Curtin

Wolff

et al. 2008

Genes Chromosomes & Cancer

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The MLH1 -93 G>A promoter polymorphism has been reported to be associated with an increased risk of microsatellite unstable colorectal cancer. Other than microsatellite instability, however, the genetic and most epigenetic changes of tumors associated with this polymorphism have not been studied. We evaluated associations between the -93 G>A polymorphism and CpG island methylator phenotype (CIMP), BRAF V600E mutations, and MLH1 methylation in tumors from a sample of 1,211 individuals with colon cancer and 1,968 controls from Utah, Northern California and Minnesota. The -93 G>A polymorphism was determined by the five prime nuclease assay. CIMP was determined previously by methylation-specific PCR of CpG islands in MLH1, methylated in tumors (MINT)1, MINT2, MINT31 and CDKN2A (p16). The BRAF V600E mutation was determined by sequencing exon 15. The MLH1 -93 G>A promoter polymorphism was associated with CIMP (odds ratio (OR) 3.44, 95% confidence interval (CI) 1.85, 6.42), MLH1 methylation (OR 4.16, 95%CI 2.20, 7.86), BRAF mutations (OR 4.26, 95%CI 1.83, 9.91) and older age at diagnosis (OR 3.65, 95%CI 2.08, 6.39) in microsatellite unstable tumors. These associations were not observed in stable tumors. Increased age at diagnosis and tumor characteristics of microsatellite unstable tumors associated with MLH1 -93 G>A suggests the polymorphism is acting at a relatively late stage of colorectal carcinogenesis to drive CIMP+ tumors down the microsatellite instability pathway.

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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"

Cited by 57 publications

References 0 publications

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Endoscopic and surgical management of serrated colonic polyps

The MLH1 −93 G>A promoter polymorphism and genetic and epigenetic alterations in colon cancer

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