Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma

Carr, Norman J.; Tan, King; Mahajan, Hema; Hawkins, Nicholas J.; Ward, Robyn L.; Nguyen, Quoc

doi:10.1097/01268031-200941001-00151

Cited by 36 publications

(59 citation statements)

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“…16,18,21,22,49,51,52 However, BRAF V600E is also found in papillary thyroid microcarcinoma, a tumor that is typically benign and often discovered as an incidental finding, as well as in pre-malignant colorectal and nevocellular lesions, suggesting that an activating mutation in BRAF occurs early in the initiation of papillary thyroid neoplasia and may additionally confer susceptibility for malignant progression. 12,17,18,[53][54][55][56] Compatible with this interpretation, one of the three tumors harboring BRAF V600E in this study was clinically indolent, whereas two behaved aggressively.…”

Section: Discussionmentioning

confidence: 68%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

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Section: Discussionmentioning

confidence: 68%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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“…In the current study, 51.1% of all patients with 1 LPD SP had 1 synchronous adenoma, at a mean (SD) age of 63 (11) years, suggesting that aging may increase the risk for having both LPD SPs and adenomas (19)(20)(21)23). Some previous studies found an association between female gender and presence of serrated polyps (9,39), whereas others, including the current study, did not (40,41). Most of these studies observing gender differences were retrospective in nature and based on histopathology data only.…”

Section: Discussionmentioning

confidence: 86%

Simple Clinical Risk Score Identifies Patients with Serrated Polyps in Routine Practice

Bouwens

Winkens

Rondagh

et al. 2013

Cancer Prevention Research

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Large, proximal, or dysplastic (LPD) serrated polyps (SP) need accurate endoscopic recognition and removal as these might progress to colorectal cancer. Herewith, we examined the risk factors for having 1 LPD SP. We developed and validated a simple SP risk score as a potential tool for improving their detection. We reviewed clinical, endoscopic, and histologic features of serrated polyps in a study of patients undergoing elective colonoscopy (derivation cohort). A self-administered questionnaire was obtained. We conducted logistic regression analyses to identify independent risk factors for having 1 LPD SP and incorporated significant variables into a clinical score. We subsequently tested the performance of the SP score in a validation cohort. We examined 2,244 patients in the derivation and 2,402 patients in the validation cohort; 6.3% and 8.2% had 1 LPD SP, respectively. Independent risk factors for LPD SPs were age of more than 50 years [OR 2.2; 95% confidence interval (CI), 1.3-3.8; P ¼ 0.004], personal history of serrated polyps (OR 2.6; 95% CI, 1.3-4.9; P ¼ 0.005), current smoking (OR 2.2; 95% CI, 1.4-3.6; P ¼ 0.001), and nondaily/no aspirin use (OR 1.8; 95% CI, 1.1-3.0; P ¼ 0.016). In the validation cohort, a SP score 5 points was associated with a 3.0-fold increased odds for LPD SPs, compared with patients with a score <5 points. In the present study, age of more than 50 years, a personal history of serrated polyps, current smoking, and nondaily/no aspirin use were independent risk factors for having LPD SPs. The SP score might aid the endoscopist in the detection of such lesions. Cancer Prev Res; 6(8); 855-63. Ó2013 AACR.

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“…24 Rare occurrence of BRAF mutations has been documented for conventional adenomas (0-5%), although they are frequent in SSA/Ps (50-90%). 4,[6][7][8][9][10][11][12][13] In contrast, KRAS mutations have shown to be rare in SSA/Ps (0-8%), but more common in conventional tubular adenomas (5-37%). 4,6,10,11,13 In our study, BRAF mutations were frequent (82%), whereas KRAS mutation was not detected in SSA/ Ps, with clearly contrasting results for tubular adenomas (BRAF mutation, 0%, KRAS mutation, 26%).…”

Section: Modern Pathology (2015) 28 146-158mentioning

confidence: 99%

“…shown associations of SSA/P and those with dysplasia or carcinoma with methylation or loss of protein expression for DNA repair genes, ie, MLH1, 1,4,6-9 a CpG island methylator phenotype, 3,4,6,8 BRAF mutations, 3,4,[6][7][8][9][10][11][12][13][14] and a lack of genetic alterations in CTNNB1 (the gene coding for b-catenin protein). 14 This pathway is thought to be distinct from the conventional adenoma-carcinoma pathway, where adenomas progress to invasive colorectal carcinomas through the influence of a series of genetic alterations including adenomatous polyposis coli (APC) and KRAS mutations.…”

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confidence: 99%

Distinct WNT/β-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum

et al. 2015

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Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated neoplasia pathway leading to colorectal cancer development. The conventional adenoma-carcinoma sequence is associated with activation of the WNT signaling pathway, although its role in serrated lesions is still controversial. To clarify differences in WNT signaling activation in association with MLH1 methylation or BRAF/KRAS mutations between serrated and conventional routes, we performed b-catenin immunostaining, methylation-specific PCR for MLH1 and WNT signaling associated genes such as AXIN2, APC, and MCC and secreted frizzled-related proteins (SFRPs), and direct sequencing of BRAF/KRAS in 27 SSA/Ps, 14 SSA/Ps with high-grade dysplasia and 9 SSA/Ps with submucosal carcinoma, as well as 19 conventional adenomas, 26 adenomas with high-grade dysplasia and 25 adenomas with submucosal carcinoma. Nuclear b-catenin labelings were significantly lower in the serrated series than in their adenoma counterparts, and a significant increment in those labelings was found from SSA/Ps to those with high-grade dysplasia or submucosal carcinoma. The frequency of MLH1 and SFRP4 methylation was significantly higher in SSA/P series, as compared with corresponding adenoma series. AXIN2 and MCC were more frequently methylated in SSA/Ps with high-grade dysplasia and those with submucosal carcinoma than in adenoma counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through those with high-grade dysplasia to those with submucosal carcinoma. A significant correlation was seen between nuclear b-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. BRAF mutation was more frequent, whereas KRAS mutation was less frequent in the SSA/P series as compared with the adenoma series. There was an inverse association of BRAF mutation with AXIN2 methylation in SSA/P series. In conclusion, WNT/b-catenin signal activation mediated by the methylation of SFRP4, MCC, and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.

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Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma

Cited by 36 publications

References 0 publications

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Simple Clinical Risk Score Identifies Patients with Serrated Polyps in Routine Practice

Distinct WNT/β-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum

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