FADD expression as a prognosticator in early-stage glottic squamous cell carcinoma of the larynx treated primarily with radiotherapy.
OBJECTIVE
We recently reported on the identification of the Fas-associated death domain (FADD) as a possible driver of the chromosome 11q13 amplicon and the association between increased FADD expression and disease-specific survival in advanced-stage laryngeal carcinoma. The aim of this study was to examine whether expression of FADD and its Ser194-phosphorylated isoform (pFADD) predicts local control in patients with early-stage glottic carcinoma primarily treated with radiotherapy only.


METHODS
Immunohistochemical staining for FADD and pFADD was performed on pretreatment biopsy specimens of 92 patients with T1-T2 glottic squamous cell carcinoma primarily treated with radiotherapy between 1996 and 2005. Cox regression analysis was used to correlate expression levels with local control.


RESULTS
High levels of pFADD were associated with significantly better local control (hazard ratio, 2.40; 95% confidence interval, 1.04-5.55; p = 0.040). FADD overexpression showed a trend toward better local control (hazard ratio, 3.656; 95% confidence interval, 0.853-15.663; p = 0.081). Multivariate Cox regression analysis showed that high pFADD expression was the best predictor of local control after radiotherapy.


CONCLUSIONS
This study showed that expression of phosphorylated FADD is a new prognostic biomarker for better local control after radiotherapy in patients with early-stage glottic carcinomas.
Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Michiel L
ML
Schrijvers
Wouter J
WJ
Pattje
Lorian
L
Slagter-Menkema
Mirjam F
MF
Mastik
Johan H
JH
Gibcus
Johannes A
JA
Langendijk
Jacqueline E
JE
van der Wal
Bernard F A M
BF
van der Laan
E
E
Schuuring
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D051356:Cortactin / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D005931:Glottis; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism
D014408:Biomarkers, Tumor; D051356:Cortactin; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D019938:Cyclin D1