Cyclin D1 and FADD as biomarkers in head and neck squamous cell carcinoma.
OBJECTIVE
Cyclin D1 and FADD (Fas-associated protein with death domain) regulate the cell cycle and apoptosis, respectively, and are located on chromosome 11q13, which is frequently amplified in head and neck squamous cell carcinoma (HNSCC). This study evaluates these proteins as predictors of clinical outcomes for HNSCC.


METHODS
Historical cohort study.


METHODS
Academic tertiary care center.


METHODS
Two hundred twenty-two patients with upper aerodigestive HNSCC.


RESULTS
Patients with tumors that were strongly positive for cyclin D1 and FADD had reduced overall (OS; P = .003 and P < .001), disease-specific (DSS; P = .039 and P < .001), and disease-free (DFS; P = .026 and P < .001) survival, respectively. Together, the 2 markers effectively stratified OS (P < .001), DSS (P < .001), and DFS (P = .002). Strong FADD staining correlated with greater alcohol consumption and varied significantly with primary tumor site: 56% of hypopharynx tumors expressed high levels of FADD but only 7% of glottis tumors. Using Cox regression analysis, FADD and N stage were significant independent predictors of DSS and DFS, whereas cyclin D1, FADD, and N stage were independently significant for OS.


CONCLUSIONS
Cyclin D1 and FADD may have utility as predictors of long-term outcomes for patients with HNSCC. Further study is needed to determine if these proteins predict response to different treatment approaches or assist in selecting patients for multimodality therapy.
Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia 22908-0713, USA.
Jk J
JJ
Rasamny
Amir
A
Allak
Kaelyn A
KA
Krook
Vickie Y
VY
Jo
Maria L
ML
Policarpio-Nicolas
Heather M
HM
Sumner
Christopher A
CA
Moskaluk
Henry F
HF
Frierson
Mark J
MJ
Jameson
D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D019938:Cyclin D1 / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D015996:Survival Rate
D015415:Biomarkers; D053200:Fas-Associated Death Domain Protein; D019938:Cyclin D1