Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas

Histopathology. 2008 Nov;53(5):567-77. doi: 10.1111/j.1365-2559.2008.03159.x.

Abstract

Aims: To evaluate the prognostic impact of expression of receptor tyrosine kinases epidermal growth factor receptor (EGFR), HER2, and C-KIT in relation to established clinicopathological parameters in salivary gland carcinomas.

Methods and results: Immunohistochemistry for EGFR, HER2, C-KIT and the proliferation marker Ki67 was performed in 101 cases of salivary gland carcinoma and related to long-term clinical follow-up. Immunopositivity of C-KIT was common in adenoid cystic carcinoma (92%). Lack of C-KIT expression occurred in salivary duct carcinoma (P < 0.001) and was associated with high-grade tumours (P = 0.002), positive lymph nodes (P = 0.002) and high expression of Ki67 (P = 0.001). HER2 was typically expressed in salivary duct carcinomas (83%), but was not associated with any other parameter. EGFR overexpression occurred independently of histological type and clinical parameters. On univariate survival analysis, overexpression of EGFR (P = 0.011) and lack of C-KIT (P = 0.014) were associated with worse prognosis, whereas HER2 was of no prognostic significance. On multivariate analysis, the strongest negative predictor of survival was high proliferative activity measured by Ki67 (P = 0.002), followed by presence of residual tumour (P = 0.006), overexpression of EGFR (P = 0.026) and advanced tumour stage (P = 0.041).

Conclusions: The expression of receptor tyrosine kinases confers additional prognostic impact on disease-specific survival. EGFR overexpression is an independent negative prognostic factor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / diagnosis
  • Carcinoma / mortality*
  • Carcinoma / pathology*
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / mortality*
  • Salivary Gland Neoplasms / pathology*
  • Survival Analysis

Substances

  • Ki-67 Antigen
  • ErbB Receptors
  • Proto-Oncogene Proteins c-kit
  • Receptor, ErbB-2