Elsevier

Pathology

Volume 45, Issue 4, June 2013, Pages 346-356
Pathology

Clinicopathological relevance of BRAF mutations in human cancer

https://doi.org/10.1097/PAT.0b013e328360b61dGet rights and content

Summary

BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia. In these cancers, various genetic aberrations of the BRAF proto-oncogene, such as different point mutations and chromosomal rearrangements, have been reported. The most common mutation, BRAF V600E, can be detected by DNA sequencing and immunohistochemistry on formalin fixed, paraffin embedded tumour tissue. Detection of BRAF V600E mutation has the potential for clinical use as a diagnostic and prognostic marker. In addition, a great deal of research effort has been spent in strategies inhibiting its activity. Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. Clinical trials are underway for other cancers. However, cutaneous side effects of treatment have been reported and therapeutic response to cancer is short-lived due to the emergence of several resistance mechanisms. In this review, we give an update on the clinical pathological relevance of BRAF mutation in cancer. It is hoped that the review will enhance the direction of future research and assist in more effective use of the knowledge of BRAF mutation in clinical practice.

References (144)

  • T. May et al.

    Low malignant potential tumors with micropapillary features are molecularly similar to low-grade serous carcinoma of the ovary

    Gynecol Oncol

    (2010)
  • R.J. Kurman et al.

    Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—shifting the paradigm

    Hum Pathol

    (2011)
  • W.S. Samowitz

    Genetic and epigenetic changes in colon cancer

    Exp Mol Pathol

    (2008)
  • A. Farina-Sarasqueta et al.

    The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

    Ann Oncol

    (2010)
  • W. De Roock et al.

    Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis

    Lancet Oncol

    (2010)
  • M. Ramanan et al.

    Paediatric brain tumours treated at a single, tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia

    J Clin Neurosci

    (2012)
  • H. Sasaki et al.

    Uncommon V599E BRAF mutations in Japanese patients with lung cancer

    J Surg Res

    (2006)
  • W. Pao et al.

    New driver mutations in non-small-cell lung cancer

    Lancet Oncol

    (2011)
  • S. Yoon et al.

    The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions

    Growth Factors

    (2006)
  • H. Davies et al.

    Mutations of the BRAF gene in human cancer

    Nature

    (2002)
  • K.P. Hoeflich et al.

    Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen- activated protein kinase pathway suppression

    Cancer Res

    (2009)
  • J.H. Lee et al.

    Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis

    Br J Dermatol

    (2011)
  • M. Colombino et al.

    BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma

    J Clin Oncol

    (2012)
  • P.M. Pollock et al.

    High frequency of BRAF mutations in nevi

    Nat Genet

    (2003)
  • G.V. Long et al.

    Prognostic and clinicopatho- logic associations of oncogenic BRAF in metastatic melanoma

    J Clin Oncol

    (2011)
  • M.T. Landi et al.

    MC1R germline variants confer risk for BRAF-mutant melanoma

    Science

    (2006)
  • S. Broekaert et al.

    Genetic and morphologic features for melanoma classification

    Pigment Cell Melanoma Res

    (2010)
  • A. Viros et al.

    Improving melanoma classification by integrating genetic and morphologic features

    PLoS Med

    (2008)
  • H. El-Osta et al.

    BRAF mutations in advanced cancers: clinical characteristics and outcomes

    PloS One

    (2011)
  • J.A. Jakob et al.

    NRAS mutation status is an independent prognostic factor in metastatic melanoma

    Cancer

    (2012)
  • E. Edlundh-Rose et al.

    NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing

    Melanoma Res

    (2006)
  • A.K. Lam et al.

    Papillary carcinoma of thyroid: A 30-yr clinicopathological review of the histological variants

    Endocr Pathol

    (2005)
  • M.N. Nikiforova et al.

    BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas

    J Clin Endocrinol Metab

    (2003)
  • Y. Cohen et al.

    Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules

    Clin Cancer Res

    (2004)
  • A. Kumagai et al.

    Low frequency ofBRAFT1796A mutations in childhood thyroid carcinomas

    J Clin Endocrinol Metab

    (2004)
  • K. Penko et al.

    BRAF mutations are uncommon in papillary thyroid cancer of young patients

    Thyroid

    (2005)
  • A. Finkelstein et al.

    Papillary thyroid carcinomas with and without BRAF? V600E mutations are morphologically distinct

    Histopathology

    (2012)
  • H. Namba et al.

    Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers

    J Clin Endocrinol Metab

    (2003)
  • K.H. Kim et al.

    Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population

    Yonsei Med J

    (2004)
  • G. Riesco-Eizaguirre et al.

    The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane

    Endocr Relat Cancer

    (2006)
  • S. Barollo et al.

    BRAF in primary and recurrent papillary thyroid cancers: the relationship with 131I and 2-[18F] fluoro-2- deoxy-d-glucose uptake ability

    Eur J Endocrinol

    (2010)
  • T.H. Kim et al.

    The association of the BRAFV600E mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer

    Cancer

    (2011)
  • A. Salajegheh et al.

    Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists

    Postgrad Med J

    (2008)
  • R.V. Lloyd et al.

    Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma

    Am J Surg Pathol

    (2004)
  • M. Cahadas-Garre et al.

    Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients

    Ann Surg

    (2012)
  • G. Salvatore et al.

    Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma

    J Clin Endocrinol Metab

    (2004)
  • J. Schmidt et al.

    BRAF in papillary thyroid carcinoma of ovary (struma ovarii)

    Am J SurgPathol

    (2007)
  • R. Flavin et al.

    BRAF T1799A mutation occurring in a case of malignant struma ovarii

    Int J Surg Pathol

    (2007)
  • E.F. Wolff et al.

    Expression of benign and malignant thyroid tissue in ovarian teratomas and the importance of multimodal management as illustrated by a BRAF-positive follicular variant of papillary thyroid cancer

    Thyroid

    (2010)
  • N. Lalwani et al.

    Histologic, molecular, and cytogenetic features of ovarian cancers: implications for diagnosis and treatment

    Radiographics

    (2011)
  • Cited by (0)

    View full text