Clinicopathological relevance of BRAF mutations in human cancer

Pakneshan, Sahar; Salajegheh, Ali; Smith, Robert A.; Lam, Alfred King‐Yin

doi:10.1097/pat.0b013e328360b61d

Cited by 141 publications

(128 citation statements)

References 142 publications

(175 reference statements)

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“…BRAF mutation was noted in approximately 45% of papillary thyroid carcinoma (Pakneshan et al 2013). It was often noted in conventional papillary thyroid carcinoma of advanced pathological stages as well as those associated with lymphocytic thyroiditis (Smith et al 2011).…”

Section: Mapk and Pi3k/act Pathways And Tertmentioning

confidence: 99%

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Lam¹,

Saremi²

2017

Endocrine-Related Cancer

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The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid. Microscopic examination of CMV-PTC revealed predominately cribriform and morular pattern of cancer cells with characteristic nuclear features of papillary thyroid carcinoma. Psammoma body is rare. On immunohistochemical studies, β-catenin is diffusely positive in CMV-PTC. The morular cells in CMV-PTC are strongly positive for CD10, bcl-2 and E-cadherin. Pre-operative diagnosis of CMV-PTC by fine-needle aspiration biopsy could be aided by cribriform architecture, epithelial morules and β-catenin immunostaining. Mutations of APC gene are found in the patients with CMV-PTC associated with FAP. In addition, mutations in CTNNB1, RET/PTC rearrangement and PI3K3CA mutations have been reported. BRAF mutation is negative in all CMV-PTC tested. Compared to conventional papillary thyroid carcinoma, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patients' mortality rates (2%). To conclude, patients with CMV-PTC have distinctive clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

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Section: Mapk and Pi3k/act Pathways And Tertmentioning

confidence: 99%

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Lam¹,

Saremi²

2017

Endocrine-Related Cancer

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“…Debemos considerar que a este grupo de pacientes inicialmente se les realizó estudio de la mutación del gen KRAS, el cual resultó ser positivo en 42%. Estas cifras son similares a las reportadas en la literatura respecto de ambos genes 24,31 , por lo cual, la frecuencia acumulativa de mutación de KAS y BRAF es de 54% en nuestro medio, cifra que podría aumentar levemente si agrega el estudio de mutaciones de otros codones de menor frecuencia del gen KRAS como 61 y 146, entre otros. Estos resultados sugieren que la terapia con anticuerpos monoclonales contra EGFR en el cáncer de colon y recto avanzado no tendría indicación en este grupo de pacientes, ya que ambos eventos serían un predictor de resistencia en más de la mitad de los pacientes.…”

Section: Discussionunclassified

“…Un hecho demostrado es que la mutación de KRAS y BRAF son mutuamente excluyentes, es decir, cuando uno de estos genes presenta una mutación el otro excepcionalmente está mutado, por lo cual, ambos eventos pertenecientes a la vía RAS-RAF-MEK-ERK-MAP quinasa han sido sólo excepcionalmente reportados en menos de 0,02% de los casos en que ambos genes han sido estudiados simultáneamente 23 . Mutaciones del gen BRAF también se ha identificado en otros tumores malignos como el carcinoma papilar de tiroides, melanoma, adenocarcinomas del ovario y leucemias, entre otros 24 .…”

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Mutación del gen BRAF en pacientes con cánceres de colon y recto con KRAS no mutado

Roa¹,

Game

Bizama³

et al. 2014

Rev. méd. Chile

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E l cáncer de colon y recto es el cuarto cán-cer de mayor incidencia y mortalidad en el mundo y representa la tercera causa de mortalidad por tumores malignos en el hombre y el quinto en la mujer 1 . En Chile ocupa el tercer lugar entre los cánceres digestivos y el séptimo a nivel global con una mortalidad de alrededor de 8 por 10 6 habitantes 2-4 . Desde el punto de vista genético-molecular, esta neoplasia ha sido extensamente caracterizada tanto en sus formas esporádicas como las hereditarias poliposas y no poliposas [5][6][7] , así como los genes que participan y vías metabólicas involucradas [8][9][10] . (Rev Med Chile 2014; 142: 55-60)

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“…12 Other common BRAF mutations in codon 600 are BRAF V600E2, V600D, V600K, V600R, and V600M. 13 BRAF V600E mutations are found in virtually all patients with hairy cell leukemia; these aberrations are also quite common in papillary thyroid cancer, malignant melanoma, and colon cancer developing via the alternative pathway. 14 Identification of KRAS and BRAF mutation carriers has gained increasing attention with the advent of targeted therapies, considered a promising treatment for human malignancies with constitutive activation of MAPK pathway and, specifically, with BRAF V600E mutation.…”

Section: Introductionmentioning

confidence: 99%

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers

et al. 2017

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Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No statistically significant relationship (p > 0.05) was found between the presence of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system Idylla™ may be also a powerful prognostic tool in subjects with newly diagnosed serous borderline tumors, identifying a subset of patients who are unlikely to progress.

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Clinicopathological relevance of BRAF mutations in human cancer

Cited by 141 publications

References 142 publications

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Mutación del gen BRAF en pacientes con cánceres de colon y recto con KRAS no mutado

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers

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