Epidermal growth factor receptor and human epidermal growth receptor 2 expression in parotid mucoepidermoid carcinoma: Possible implications for targeted therapy

Abstract

Abstract. The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) was analyzed in immunohistochemical preparations from 46 primary parotid mucoepidermoid carcinomas (MEC). For the cases with lymph node metastases, the receptor expressions were investigated in parallel samples, primary tumour and metastasis, from each patient (n=11). The goal was to evaluate whether any of these receptors are suitable as a target for radionuclide-based imaging and therapy. The HercepTest scoring was used for the analysis of both HER2 and EGFR expression (0, 1+, 2+ or 3+). EGFR overexpression (2+/3+) was found in 67.4% (31/46) of the primary tumours. Out of the 11 cases with evaluated paired samples, EGFR overexpression was observed in 81.8% (9/11) of the primary tumours and 72.7% (8/11) of the corresponding lymph node metastases. There was only one patient who had EGFR overexpression in the primary tumours which changed to negative in the lymph node metastases but no changes occurred reciprocally. The HER2 overexpression was only found in 4.3% (2/46) of the primary mucoepidermoid carcinoma and none of the lymph node metastases (0/11). EGFR and HER2 stainings were mainly found in the cell membranes. It was concluded that the majority of parotid mucoepidermoid carcinomas express EGFR strongly in their cell membranes and that lymph node metastases generally express EGFR to approximately the same extent as in the primary tumours. The stability in the EGFR expression is encouraging in the effort to develop radionuclide-based EGFR imaging agents. It is also possible that EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabelled antibodies) can be applied for the therapy of mucoepidermoid carcinoma.

Immunohistochemical correlation of epidermal growth factor receptor and c-erbB-2 with histopathologic grading of mucoepidermoid carcinoma

“…[13] In the present study the mean of EGFR expression was 71%. [1,12,14] Hoyeck-Gebily found a positive correlation between histopathologic grading of MEC and EGFR expression, which is consistent with our results with a similar correlation (P = 0.001). [1] A review of literature shows an obvious controversy regarding the c-erbB-2 expression in MEC.…”

“…[30] A high frequency of EGFR overexpression has been reported in cancers of the head and neck region. [12] Generally, it is accepted that the overexpression of EGFR is common in salivary gland carcinomas, although in an earlier study with a small sample size, the incidence of positive EGFR staining was found to be 25% in mucoepidermoid carcinoma. [13] In the present study the mean of EGFR expression was 71%.…”

“…[25,27,28] Furthermore, studies have reported contradictory results regarding correlation between expression of some immunohistochemical markers such c-erbB-2 with histopathologic grades. [11][12][13]17,18,25,29] On the other hand a few studies have been done about correlation of EGFR with grading of mucoepidermoid carcinoma. [1,16] Therefore, the aim of the present study was to evaluate the immunohistochemical expression of c-erbB-2, EGFR in MEC and their correlation with histopathologic grades.…”

“…et al,Shang et al, and Sugano et al, in their studies on MEC found c-erbB-2 expression in only 4.5%, 4.3% and 0% of the cases, respectively [12,18,31]. However, Weed et al,Cho et al, and Press et al, reported c-erbB-2 overexpression in 25%, 36% and 38% of the cases studied.…”

“…[10] Overexpression or amplification of c-erbB-2 has been documented in different human tumors, mostly adenocarcinoma of the stomach, ovaries, breast, kidney and salivary glands, and has shown association with a poor prognosis in some tumors. [10,11] Although some studies have examined the frequency of EGFR overexpression in salivary gland tumors, [12][13][14][15] few studies have been carried out about the correlation of this protein with grading of mucoepidermoid carcinoma. [1,16] On the other hand, controversial results have been reported about c-erbB-2 in mucoepidermoid carcinoma, with reported rates ranging from absent to 38%.…”