PMID- 12148857
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20151119
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 112
IP  - 3
DP  - 2002 Mar
TI  - Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor 
      prognosis in head and neck tumors.
PG  - 472-81
AB  - OBJECTIVES/HYPOTHESIS: Cyclin D1, a cell cycle regulator localized to chromosome 
      11q13, is amplified in several human tumors including head and neck squamous cell 
      carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been 
      correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has 
      also been observed in a significant proportion of HNSCC. The p16 gene regulates 
      cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene 
      phosphorylation, thereby downregulating cellular proliferation. Detection of 
      cyclin D1 amplification and p16 deletion using a simple and sensitive method will 
      be valuable for the development of effective treatment modalities for head and 
      neck cancer. STUDY DESIGN: We have used fluorescence in situ hybridization (FISH) 
      to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. 
      Both single- and dual-color FISH were performed. METHODS: Paraffin-embedded 
      tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for 
      cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 
      centromeric probes as a control. Twenty-eight of these samples were analyzed for 
      p16 expression by immunohistochemistry. RESULTS: Cyclin D1 amplification was 
      observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of 
      p16 expression was observed in 64% (18/28) of patients. There was a good 
      correlation between the deletion of p16 sequences and the loss of p16 expression 
      (P = .008). Amplification of cyclin D1 had a statistically significant 
      association with recurrence, distant metastasis, and survival at 36 months. There 
      was a significant association between p16 deletion and the development of distant 
      metastases. Cyclin D1 amplification and p16 deletion together correlated with 
      recurrence, distant metastasis, and survival. CONCLUSIONS: We demonstrate that 
      FISH is a simple and sensitive method for detecting cyclin D1 amplification and 
      p16 deletion in head and neck cancer. Our results suggest that these two genetic 
      aberrations together portend a poorer outcome than either of the abnormalities 
      alone in head and neck cancer.
FAU - Namazie, Ali
AU  - Namazie A
AD  - Division of Head and Neck Surgery, University of California Los Angeles School of 
      Medicine, USA.
FAU - Alavi, Sassan
AU  - Alavi S
FAU - Olopade, Olufunmilayo I
AU  - Olopade OI
FAU - Pauletti, Giovanni
AU  - Pauletti G
FAU - Aghamohammadi, Neema
AU  - Aghamohammadi N
FAU - Aghamohammadi, M
AU  - Aghamohammadi M
FAU - Gornbein, Jeffrey A
AU  - Gornbein JA
FAU - Calcaterra, Thomas C
AU  - Calcaterra TC
FAU - Slamon, Dennis J
AU  - Slamon DJ
FAU - Wang, Marilene B
AU  - Wang MB
FAU - Srivatsan, Eri S
AU  - Srivatsan ES
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Carcinoma, Squamous Cell/*genetics/metabolism
MH  - Chi-Square Distribution
MH  - Cyclin D1/*genetics/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism
MH  - Female
MH  - Gene Amplification
MH  - Gene Deletion
MH  - Head and Neck Neoplasms/*genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Survival Analysis
EDAT- 2002/08/01 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/08/01 10:00
PHST- 2002/08/01 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/08/01 10:00 [entrez]
AID - 10.1097/00005537-200203000-00013 [doi]
PST - ppublish
SO  - Laryngoscope. 2002 Mar;112(3):472-81. doi: 10.1097/00005537-200203000-00013.