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Original Articles
Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal Cancer Harboring BRAF V600E Mutation
Jeong-Hwa Kwon, Byung-Kwan Jeong, Yong Sik Yoon, Chang Sik Yu, Jihun Kim
J Pathol Transl Med. 2018;52(3):157-163.   Published online March 29, 2018
DOI: https://doi.org/10.4132/jptm.2018.03.28
  • 6,260 View
  • 166 Download
  • 6 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary Material
Background
BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing for every CRC case is not cost-effective. An antibody specific for BRAF V600E mutant protein has been introduced, and we thus examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC.
Methods
Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs between 2005 and 2015 were selected from the archives of Asan Medical Center. Tissue microarrays were constructed and stained with BRAF VE1 antibody.
Results
Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild-type cases also stained positive with BRAF VE1 antibody; four stained weakly and two stained moderately. Normal colonic crypts showed nonspecific weak staining, and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF wild-type patients.
Conclusions
BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasional nonspecific staining in tumor cell nuclei and normal colonic crypts may limit their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful screening tool for BRAF V600E mutation in CRCs, provided that additional sequencing studies can be done to confirm the mutation in BRAF VE1 antibody-positive cases.

Citations

Citations to this article as recorded by  
  • Immunohistochemistry as a Surrogate Marker of Underlying Molecular Derangements in Sporadic Colorectal Carcinoma in Children – A Series of Three Cases
    Priyanka Maity, Aniket Halder, Ranajoy Ghosh, Uttara Chatterjee, Shibsankar Barman, Ruchirendra Sarkar
    Fetal and Pediatric Pathology.2022; 41(1): 98.     CrossRef
  • Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer
    Spring Holter, Michael J. Hall, Heather Hampel, Kory Jasperson, Sonia S. Kupfer, Joy Larsen Haidle, Maureen E. Mork, Selvi Palaniapppan, Leigha Senter, Elena M. Stoffel, Scott M. Weissman, Matthew B. Yurgelun
    Journal of Genetic Counseling.2022; 31(3): 568.     CrossRef
  • Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review
    Rogelio González-González, Sandra López-Verdín, Jesús Lavalle-Carrasco, Nelly Molina-Frechero, Mario Isiordia-Espinoza, Ramón G Carreón-Burciaga, Ronell Bologna-Molina
    World Journal of Clinical Oncology.2020; 11(1): 31.     CrossRef
  • Genetic and histopathological analysis of a case of primary intraosseous carcinoma, NOS with features of both ameloblastic carcinoma and squamous cell carcinoma
    Akane Yukimori, Maiko Tsuchiya, Akane Wada, Yasuyuki Michi, Kou Kayamori, Kei Sakamoto, Tohru Ikeda
    World Journal of Surgical Oncology.2020;[Epub]     CrossRef
Galectin-3 Expression and BRAF Mutation in Cases of Cytologically Suspicious Papillary Thyroid Carcinoma.
Dokyung Kim, Hyunki Kim, Jinyoung Kwak, Minju Kim, Hyung Jae Jung, Ja Seung Koo, Beom Jin Lim, Chankwon Jung, SoonWon Hong
Korean J Pathol. 2010;44(2):191-198.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.191
  • 3,388 View
  • 23 Download
AbstractAbstract PDF
BACKGROUND
Fine needle aspiration, which is known as the most accurate and cost-effective method for diagnosis of thyroid nodule, still may result in indeterminate cases that are pauci-cellular and show minor nuclear atypia, but most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs and galectin-3 was expressed by malignant tumors, helping us to differentiate malignancies from benign lesions.
METHODS
Cases studied included histologically 44 confirmed PTC cases and 18 benign cases previously diagnosed as suspicious of PTC using cytologic examination. Cases were analyzed for galectin-3 expression by immunohistochemical staining and BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme.
RESULTS
All 44 cases of PTC and 8 of 18 benign controls expressed galectin-3. BRAF mutations were found in only 9 of the 44 PTC cases. Assessment of galectin-3 expression demonstrated high sensitivity but low specificity. Evaluation of BRAF mutation revealed high specificity and low sensitivity.
CONCLUSIONS
This study suggests that the combined application of these two methods for PTC of suspicious cytology is complementary.

J Pathol Transl Med : Journal of Pathology and Translational Medicine