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Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas

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Abstract

Objectives

Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors.

Materials and methods

This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS.

Results

In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient’s age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13.

Conclusion

Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs.

Clinical relevance

The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

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Conflict of interest

The authors certify that there are no conflicts of interest with any financial organizations regarding the material discussed in the manuscript.

Author’s contributions

TS is responsible for the immunohistochemical and molecular genetic studies and draft of the manuscript.

AS is responsible for the critical interpretation of the histopathological data and participated in the design of the study.

SH participated in the design of the study.

AR is responsible for the critical revision of the results and final approval to the manuscript.

UMR conceived the study and participated in its design and coordination and helped to draft the manuscript.

CL conceived retrievement of patient data and statistical analysis.

RB is responsible for the collection of references.

FB is responsible for the text revision.

AK is responsible for the revision of the final version.

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Authors and Affiliations

  1. Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany

    T. Schneider, C. Linz, R. Brands, S. Hartmann, F. Beckford, A. C. Kübler & U. D. A. Müller-Richter

  2. Institute for Pathology, University Hospital Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

    A. Strehl & A. Rosenwald

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Schneider, T., Strehl, A., Linz, C. et al. Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas. Clin Oral Invest 20, 541–551 (2016). https://doi.org/10.1007/s00784-015-1541-1

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