Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 317-325 |
| Number of pages | 9 |
| Journal | Journal of Pathology |
| Volume | 204 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Nov 2004 |
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Keywords
- Cooperative signalling
- Head and neck
- Immunity
- Nuclear translocation
- Overexpression
- Squamous cell carcinoma
- Type I receptor tyrosine kinases
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. / 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, Raffaela.
In: Journal of Pathology, Vol. 204, No. 3, 11.2004, p. 317-325.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients
AU - Bei, Roberto
AU - Budillon, Alfredo
AU - Masuelli, Laura
AU - Cereda, Vittore
AU - Vitolo, Domenico
AU - Di Gennaro, Elena
AU - Ripavecchia, Vanessa
AU - Palumbo, Camilla
AU - Ionna, Franco
AU - Losito, Simona
AU - Modesti, Andrea
AU - Kraus, Matthias H.
AU - Muraro, Raffaela
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Cooperative signalling
KW - Head and neck
KW - Immunity
KW - Nuclear translocation
KW - Overexpression
KW - Squamous cell carcinoma
KW - Type I receptor tyrosine kinases
UR - http://www.scopus.com/inward/record.url?scp=7244232712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7244232712&partnerID=8YFLogxK
U2 - 10.1002/path.1642
DO - 10.1002/path.1642
M3 - Article
C2 - 15476268
AN - SCOPUS:7244232712
VL - 204
SP - 317
EP - 325
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 3
ER -