Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component
Ueda M. Matsuda K. Kurohama H. Mussazhanova Z. Sailaubekova Y. Kondo H. Shimizu T. Takada N. Matsuoka Y. Otsubo C. Sato S. Yamashita H. Kawakami A. Nakashima M.
August 2022MDPI
Cancers
2022#14Issue 15
Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.
53BP1 , DNA damage response , genomic instability , immunofluorescence , Ki-67 , nodule-in-nodule , NRAS , poorly differentiated component , thyroid
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Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan
Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan
Department of Diagnostic Pathology, Nagasaki University Hospital, Nagasaki, 852-8501, Japan
High Medical School, Faculty of Medicine and Health Care, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan
Medical Student Research Program, Nagasaki University School of Medicine, Nagasaki, 852-8523, Japan
Medical Student Research Program, Oita University School of Medicine, Oita, 879-5593, Japan
Yamashita Thyroid Hospital, Fukuoka, 812-0034, Japan
Department of Tumor and Diagnostic Pathology
Department of Endocrinology and Metabolism
Department of Diagnostic Pathology
High Medical School
Biostatistics Section
Medical Student Research Program
Medical Student Research Program
Yamashita Thyroid Hospital
10 лет помогаем публиковать статьи Международный издатель
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