Joint research project of genetic diagnosis of papillary thyroid cancer between Semipalatinsk Medical Academy and Nagasaki University

Abstract

The activating point mutation of BRAF gene, BRAF T1799A , is the most common and specific genetic alteration in adult papillary thyroid carcinoma. BRAF T1799A seems to be associated with clinical aggressiveness of papillary thyroid carcinoma. We have established that PCR-RFLP method enables us to detect the BRAF T1799A mutation using DNA extracted from fine-needle aspiration biopsy samples and then applied this proprietary method not only to our clinical practice but also to international medical assistance around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy cases from Japan and one hundred cases from Kazakhstan were examined. There were 14 Japanese and 50 Kazakhstani cases of cytological malignant tumors in all of the examined samples, among which we detected 12 and 14 cases with BRAF T1799A in Japanese and Kazakhstan cases, respectively. Of these cases, we found mutations in two cytological “suspicious” cases and even two pathological “benign” cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those four, were confirmed as papillary thyroid carcinoma by careful pathological examination including immunohistochemical analysis. In conclusion, our PCR-RFLP method for BRAF T1799A detection using fine-needle aspiration biopsy samples is useful not only for preoperative diagnosis but also for accurate pathological decision of difficult cases as a complementary diagnostic method even after surgery. The introduction of appropriate genetic evaluation together with cytological cancer diagnosis into Kazakhstan makes a novel possibility for our future joint project.