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Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients
Author(s) -
Bei Roberto,
Budillon Alfredo,
Masuelli Laura,
Cereda Vittore,
Vitolo Domenico,
Di Gennaro Elena,
Ripavecchia Vanessa,
Palumbo Camilla,
Ionna Franco,
Losito Simona,
Modesti Andrea,
Kraus Matthias H,
Muraro Raffaella
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1642
Subject(s) - cancer research , receptor , epidermal growth factor receptor , biology , erbb , head and neck squamous cell carcinoma , erbb4 , antibody , immunohistochemistry , immune system , pathology , medicine , cancer , immunology , head and neck cancer , receptor tyrosine kinase , biochemistry , genetics
In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma (HNSCC), expression abnormalities and subcellular localization of epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases. Although tumour‐specific overexpression affected each ErbB receptor (EGFR 47%, ErbB2 29%, ErbB3 21%, ErbB4 26%), EGFR abnormalities were most prevalent. The latter, and overexpression of more than two ErbB receptors in the same tumour, which always included EGFR, correlated with metastatic disease. ErbB products were specifically detected on the cell membrane and in the cytoplasm. In contrast, ErbB4 was uniquely localized to the nucleus in 7 carcinomas and a tumour‐derived cell line, indicating a role for regulated intramembrane proteolysis resulting in nuclear ErbB4 translocation in HNSCC. Expression of prototype ligand EGF or low‐affinity stromal activator tenascin correlated significantly with EGFR overexpression, implying chronic EGFR activation. Simultaneous overexpression of additional ErbB receptors in most of these cases suggested recurrent involvement of receptor heterodimers. In spite of frequent ErbB receptor alterations, autologous ErbB serum antibodies were rare, with only 1 of 38 tumour patients exhibiting an ErbB2‐specific immune response. Based on upregulation of several known immunosuppressive molecules, scarcity of ErbB‐specific antibodies is consistent with attenuation of natural tumour‐specific immune responses in HNSCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.