Use of combination proteomic analysis to demonstrate molecular similarity of head and neck squamous cell carcinoma arising from different subsites.
OBJECTIVE
To evaluate head and neck squamous cell carcinomas (HNSCCs) for differences in protein expression between oral cavity, oropharynx, larynx, and hypopharynx subsites.


METHODS
Retrospective proteomic analysis using tissue microarray (TMA) and 2-dimensional difference gel electrophoresis (2D-DIGE). For the TMA, automated quantitative protein expression analysis was used to interrogate levels of 4 cell-cycle regulatory proteins chosen for their known roles in cancer (cyclin D1, p53, Rb, and p14). For the 2D-DIGE, lesional and normal adjacent tissues were enriched by laser capture microdissection. Total protein was extracted, analyzed by 2D-DIGE with saturation dye labeling, and evaluated for relative abundance levels of individual protein spots.


METHODS
Two tertiary-care academic medical centers.


METHODS
Seventy-one patients with HNSCC for TMA, and 14 patients with HNSCC with frozen tumor and normal tissue for 2D-DIGE.


RESULTS
The automated quantitative analysis of protein expression analysis revealed no difference between subsite for cyclin D1, p53, Rb, or p14 expression. The 2D-DIGE study was based on 28 gels (14 cancer gels and 14 adjacent normal gels), and 732 spots were identified as matching across more than 90% of gels. Significance was evaluated based on false discovery rate (FDR) estimated from permuted data sets. There were no significant differences in protein expression between subsites (FDR greater than or equal to 30% in all instances).


CONCLUSIONS
Observed differences in outcomes between HNSCCs from different subsites may not reflect differences in tumor biologic characteristics between subsites. Rather, it is possible that observed clinical heterogeneity among HNSCCs may be based on other factors, such as viral vs chemical carcinogenesis.
Weinberger
Paul M
PM
Department of Otolaryngology, Institute for Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Merkley
Mark
M
Lee
Jeffrey R
JR
Adam
Bao-Ling
BL
Gourin
Christine G
CG
Podolsky
Robert H
RH
Haffty
Bruce G
BG
Papadavid
Evangelia
E
Sasaki
Clarence
C
Psyrri
Amanda
A
Dynan
William S
WS
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D040081:Protein Array Analysis; D040901:Proteomics
D008565:Membrane Proteins