Molecular marker expression in oral and oropharyngeal squamous cell carcinoma.
OBJECTIVE
To determine the relative prognostic value of p53, cyclin D1, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) expression in patients with oral and oropharyngeal squamous cell carcinoma.


METHODS
Retrospective cohort study.


METHODS
Fifty-six patients with oral and oropharyngeal squamous cell carcinoma referred to the Department of Therapeutic Radiology at Yale-New Haven Hospital (Conn) between 1981 and 1992 who were treated with gross total surgical resection and postoperative external beam radiotherapy.


RESULTS
Archival tumor tissue was stained with monoclonal antibodies directed against these 4 oncoproteins and scored for staining intensity and percent distribution by a pathologist blinded to the patients' clinical outcomes. Frequency of marker expression was 48% for p53, 20% for cyclin D1, 64% for EGFR, and 41% for VEGF. In multivariate analysis, EGFR positivity was protective against locoregional relapse (relative risk [RR], 0.27; 95% confidence interval [CI], 0.11-0.66; P =.002). In contrast, advanced N stage predicted poor locoregional relapse-free survival (RR, 1.94; 95% CI, 1.03-3.66; P =.04). Predictors of poor overall survival in multivariate analysis included VEGF positivity (RR, 3.53; 95% CI, 1.75-7.13; P<.001) and black race (RR, 2.48; 95% CI, 1.05-5.85; P =.04). Cyclin D1 and p53 expression were not significantly associated with prognosis in this cohort.


CONCLUSIONS
In oral and oropharyngeal squamous cell carcinoma treated with surgery and postoperative radiotherapy, VEGF and EGFR expression may influence clinical outcome. If confirmed, these results have potential implications for the determination of patient prognosis and the development of biologically based pharmacotherapies.
Smith
B D
BD
Department of Therapeutic Radiology, Yale University School of Medicine, PO Box 208040, New Haven, Conn 06520-8040, USA.
Smith
G L
GL
Carter
D
D
DiGiovanna
M P
MP
Kasowitz
K M
KM
Sasaki
C T
CT
Haffty
B G
BG
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D015331:Cohort Studies; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019938:Cyclin D1; D066246:ErbB Receptors