Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma.
OBJECTIVE
The role of HER-2/neu in squamous cell carcinoma (SCC) of the head and neck is not well defined. The purpose of the current study is to measure the frequency of HER-2/neu expression, to demonstrate HER-2/neu gene amplification in the cases found to be positive for protein overexpression, and to investigate the prognostic significance of overexpression and/or amplification in SCC of the head and neck.


METHODS
A cohort of 77 patients with SCC of the oral cavity or oropharynx, with stage III or IV disease and uniformly treated with surgical resection and postoperative radiation, served as the primary patient population for the study. Of these, 56 patients had adequate follow-up and paraffin-embedded specimens available for analysis. Median follow-up was 6.1 years. Each of the paraffin-embedded specimens were immunohistochemically stained for HER-2/neu expression and graded for intensity of staining by a pathologist. All cases that demonstrated positive staining by immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH) to assess HER-2/neu amplification status.


RESULTS
Five-year survival for the 56 evaluable patients was 40%, with 25% experiencing local relapse, 18% regional relapse, and 25% distant relapse. The percentage of tumors staining positive for HER-2/neu by immunohistochemistry was 17%. There was no statistically significant correlation between HER-2/neu and T stage, N stage, tumor grade, survival, or disease-free survival. HER-2/neu expression did correlate with vascular endothelial growth factor expression. FISH analysis revealed four cases that were amplified for HER-2/neu. Of note, of the 4 amplified cases, 2 suffered regional relapse, 1 suffered distant metastasis, and all 4 expired by 5 years of follow-up.


CONCLUSIONS
This is the first demonstration of HER-2/neu gene amplification by FISH in SCC of the head and neck. FISH validates a previously contested controversial role for HER-2/neu gene overexpression in SCC of the head and neck. The prognostic significance and clinical implications of HER-2/neu expression and amplification in head and neck cancer will require additional studies.
Khan
Atif J
AJ
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA.
King
Bonnie L
BL
Smith
Benjamin D
BD
Smith
Grace L
GL
DiGiovanna
Michael P
MP
Carter
Darryl
D
Haffty
Bruce G
BG
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors