Fluorescence in situ hybridization for detecting genomic alterations of cyclin D1 and p16 in oral squamous cell carcinomas.
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.
Uzawa
Narikazu
N
Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. n-uzawa.mfs@tmd.ac.jp
Sonoda
Itaru
I
Myo
Kunihiro
K
Takahashi
Ken-Ichiro
K
Miyamoto
Ryozo
R
Amagasa
Teruo
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D012008:Recurrence
D019938:Cyclin D1