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.
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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.