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Fluorescence in situ hybridization for detecting genomic alterations of cyclin D1 and p16 in oral squamous cell carcinomas
Author(s) -
Uzawa Narikazu,
Sonoda Itaru,
Myo Kunihiro,
Takahashi KenIchiro,
Miyamoto Ryozo,
Amagasa Teruo
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23030
Subject(s) - fluorescence in situ hybridization , medicine , cyclin d1 , cancer , comparative genomic hybridization , cancer research , pathology , oncology , gene , biology , cell cycle , genome , genetics , chromosome
BACKGROUND Cyclin D1 ( CCND1 ) and p16 alterations have been detected in oral squamous cell carcinomas (SCCs), suggesting that abnormalities of these genes may play an important role in the genesis or progression of oral SCCs and serve as independent prognostic indicators. The detection of CCND1 and p16 aberrations using a simple and sensitive method would be valuable for the development of effective treatment modalities for oral cancer. The objective of the current study was to determine whether CCND1 numerical aberrations and p16 deletions in oral SCCs detected by fluorescence in situ hybridization (FISH) have any impact on clinical outcome. METHODS Using genomic DNA probes for CCND1 and p16 , FISH was performed on specimens that were obtained by fine‐needle aspiration (FNA) from 57 primary oral SCCs. RESULTS The CCND1 numerical aberration was observed in 28 of 57 patients (49%) with oral SCCs and was associated significantly with reduced disease‐free survival ( P = .0004) and overall survival ( P = .0179). Conversely, p16 deletion was detected in 22 of 57 patients (39%). The disease‐free and overall survival rates for patients with p16 deletion were lower than those among patients without the p16 deletion, although the difference just failed to reach statistical significance ( P = .0516 and P = .1878, respectively). The p16 deletion in the presence of the CCND1 numerical aberration conferred significantly worse disease‐free survival ( P = .0002) and overall survival ( P = .0153). CONCLUSIONS Although the CCND1 numerical aberration was a good predictor of aggressive tumors, recurrence, and poor prognosis in patients with oral SCCs, the authors were able to identify subgroups of patients that had early disease recurrence and a poor prognosis more efficiently by assessment of p16 deletion in addition to CCND1 genetic status using FISH on FNA biopsy samples compared with the analysis of either alteration alone. Cancer 2007. © 2007 American Cancer Society.