Clinical Implications of Pre-Operative Rapid BRAF Analysis for Papillary Thyroid Cancer

Abstract

Abstract. The activating point mutation of the BRAF gene, BRAF T1799A , is the most common and specific genetic alteration in adult papillary thyroid carcinoma (PTC) and a possible marker of malignant potential of PTC. We have applied the PCR-RFLP method using fine-needle aspiration biopsy samples not only to our clinical practice but also to the international medical assistance effort around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy-seven cases (100 nodules) from Japan and 131 cases (137 nodules) from Kazakhstan were examined. There were 14 Japanese and 76 Kazakhstani cases of cytological malignant tumors from the examined samples. We detected 12 (85.7% of PTC) and 19 (25% of PTC) cases with BRAF T1799A among the Japanese and Kazakhstani cases, respectively. Of these cases, we found mutations in one cytologically "suspicious" case and even in two pathologically "benign" cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those three, were confirmed as PTC by careful pathological examination, including immunohistochemical analysis. In summary, our PCR-RFLP method for BRAF T1799A detection using FNAB samples is useful not only for preoperative diagnosis of PTC but also as a complementary diagnostic tool for accurate pathological diagnosis, even after surgery.

BRAF V600E mutation analysis increases diagnostic accuracy for papillary thyroid carcinoma in fine-needle aspiration biopsies

“…Recently, a new molecular marker has been found to increase the accuracy of FNAB cytological examination. Indeed, BRAF mutation analysis of FNAB has been reported to have high diagnostic specificity to detect PTC in previous studies examining 1153 FNAB samples with different techniques, such as RFLP, direct sequencing, pyrosequencing, real-time allele-specific amplification, and mutant allele-specific PCR amplification (3)(4)(5)(6)(7)(8)(9)(10)(11). In the present study, 469 FNAB samples, obtained from suspicious thyroid nodules, were analyzed for BRAF V600E mutation by direct sequencing and RFLP.…”

“…Point mutations in the BRAF gene, implicated in the neoplastic transformation of follicular cells, represent a specific molecular marker for papillary thyroid carcinoma (PTC) and PTC-derived cancers, characterizing up to 45% of PTCs. Previous studies have evaluated the presence of BRAF V600E mutation in FNAB from suspected thyroid nodules, with a prevalence of 62% mutated BRAF PTCs and variable sensitivity and specificity due to differences in the population studied and to the experimental methods employed (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The aim of the present study is to evaluate whether BRAF V600E mutation analysis could increase the diagnostic accuracy of FNAB for PTC in suspicious thyroid nodules of patients referred to a single institution.…”

Molecular analysis of thyroid tumors

“…The results of BRAF testing in 2766 FNA samples have been reported in 18 prospective and retrospective studies. 65,66,69,70,[79][80][81][82][83][84][85][86][87][88][89][90][91][92] Among 581 BRAF-positive nodules tested in FNA samples in these studies, 580 were papillary carcinomas on pathological examination of the resected nodules, whereas one was diagnosed as a benign nodule, 92 resulting in the false-positive rate of 0.2%. This reportedly benign nodule had a histopathological diagnosis of 'atypical nodular hyperplasia' and was not examined using modern immunohistochemical techniques that are helpful in the diagnosis of thyroid malignancy in difficult cases.…”

Possible Involvement of BRAFV600E in Altered Gene Expression in Papillary Thyroid Cancer

“…1B [12]). The high prevalence of BRAFV600E (89.5%) was more than expected, however, it should be noted that recent study by Kumagai et al have also reported similar prevalence of BRAF somatic mutation in Japanese patients [13]. Alternatively, the high prevalence may reflect relative enrichment of advanced PTCs in the specimens analyzed in the present study, although there are some controversies in the correlation between BRAF mutation and aggressiveness of PTC [14,15].…”