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Quantitative immunohistochemical analysis of transforming growth factor‐α and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck
Author(s) -
Grandis Jennifer Rubin,
Melhem Mona F.,
Barnes E. Leon,
Tweardy David J.
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960915)78:6<1284::aid-cncr17>3.0.co;2-x
Subject(s) - immunohistochemistry , immunostaining , pathology , medicine , epidermal growth factor receptor , transforming growth factor , basal (medicine) , staining , cancer , epidermal growth factor , carcinoma , receptor , insulin
BACKGROUND Transforming growth factor‐α (TGF‐α) and epidermal growth factor receptor (EGFR) mRNA are up‐regulated in squamous cell carcinoma of the head and neck (SCCHN) tissues. METHODS Immunohistochemical staining with monoclonal antibodies to TGF‐α and EGFR was undertaken to identify the cellular origin in tissue obtained from cancer patients and controls and to determine the correlation between mRNA expression levels and two methods of immunohistochemical evaluation. RESULTS TGF‐α protein staining occurred in the suprabasal layers and spared the basal layer of normal controls. Conversely, in histologically normal mucosa from SCCHN patients, TGF‐α was present throughout the epithelium, including the basal layer. EGFR staining was negligible in normal mucosa from control patients without cancer and relatively increased in SCCHN tissues. Increasing staining intensity was correlated with worsening dysplasia and closer proximity to the tumor. Using computerized image analysis to quantify the intensity of immunostaining, the mean optical density (MOD) of TGF‐α staining in histologically normal mucosa ( P = 0.049) and tumors ( P = 0.005) from SCCHN patients was significantly higher than in control normal mucosa from noncancer patients (1.9‐ and 1.7‐fold, respectively). EGFR MOD was also greater in the histologically normal mucosa ( P = 0.009) and tumors ( P = 0.006) from SCCHN patients than in control normal mucosa (1.8‐ and 1.9‐fold, respectively). For both TGF‐α ( P = 0.668) and EGFR ( P = 0.116), the MOD was similar for both tumor and histologically normal mucosa from SCCHN patients. CONCLUSIONS TGF‐α and EGFR protein expression is increased early in head and neck squamous cell carcinogenesis and can be quantitated by computerized image analysis of immunohistochemical staining. Altered distribution of TGF‐α protein in histologically normal mucosa from SCCHN patients compared with control mucosa from patients without cancer suggests a switch from a paracrine to an autocrine pathway. Cancer 1996;78:1284‐92.