Clinical impact of a cytological screening system using cyclin D1 immunostaining and genomic analysis for the diagnosis of thyroid nodules.

Research Project

Project/Area Number	17K16951
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Otorhinolaryngology
Research Institution	Kobe University
Principal Investigator	Masanori Teshima 神戸大学, 医学部附属病院, 講師 (10749146)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	甲状腺結節 / スクリーニング / 細胞診 / cyclin D1 / 次世代シークエンサー / 診断 / 甲状腺腫瘍 / 治療 / 甲状腺癌 / 遺伝子診断
Outline of Final Research Achievements	One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P<0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P<0.001). Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.
Academic Significance and Societal Importance of the Research Achievements	特に甲状腺細胞診診断が困難な施設において、良性、悪性の鑑別困難な甲状腺結節の術前診断を行う際には、Cyclin D1免疫染色を用いた細胞診を行うことが腫瘍性病変スクリーニングの手段の一つとなる。特に陰性の結節であった場合は腺腫様結節の診断であり、経過観察とすることができるため、診断目的の手術を減らす一助となる可能性がある。