TERT promoter mutations and Ki-67 labeling index as a prognostic marker of papillary thyroid carcinomas: combination of two independent factors.
Although most papillary thyroid carcinomas (PTCs) have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed. In the present study, we assessed the impact of the combination of the TERT promoter/BRAF mutations and Ki-67 labeling index (LI) as a prognostic marker in PTC patients. Of 400 PTC samples, 354 were successfully genotyped for both TERT promoter/BRAF and analyzed for Ki-67 LI. Based on the combination of the mutational status and Ki-67 LI, the cases were categorized into three groups: high-, middle-, and low-risk. The recurrence rates of low-, middle-, and high-risk group were 1.9% (6 of 323), 18.2% (4 of 22), and 44.4% (4 of 9), respectively. The Kaplan-Meier curve and log-rank analyses demonstrated that there were statistical differences between any two groups. The hazard ratios for recurrence remained significant after adjustment for age, sex, tumor size, and extrathyroidal extension (low vs. middle: 8.80, 95% CI: 2.35-32.92, p = 0.001; middle vs. high: 6.255, 95% CI: 1.13-34.51, p = 0.035). In conclusion, the combination of the TERT promoter/BRAFV600Emutations and Ki-67 LI performed excellent in predicting PTC recurrence and may be clinically useful.
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Michiko
M
Matsuse
Department of Surgery, Kuma Hospital, Kobe, Japan.
Tomonori
T
Yabuta
Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki Japan.
Vladimir
V
Saenko
Department of Diagnostic Pathology, Kuma Hospital, Kobe, Japan.
Mitsuyoshi
M
Hirokawa
Department of Internal Medicine, Kuma Hospital, Kobe, Japan.
Eijun
E
Nishihara
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Keiji
K
Suzuki
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.|Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki Japan.
Shunichi
S
Yamashita
Department of Surgery, Kuma Hospital, Kobe, Japan.
Akira
A
Miyauchi
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Norisato
N
Mitsutake
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012008:Recurrence; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase