Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

Abstract

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status. Keywords: salivary gland-type lung carcinoma; adenoid cystic carcinoma; mucoepidermoid carcinoma; epidermal growth factor receptor; immunohistochemistry; FISH Salivary gland-type lung carcinomas are uncommon, representing less than 1% of all lung tumors. Adenoid cystic carcinoma and mucoepidermoid carcinoma are the two most common subtypes. 1,2 Salivary gland-type lung carcinomas are generally reported as having a good prognosis. Indeed, mucoepidermoid carcinoma usually presents as a localized disease that can be completely resected with surgery and the reported 5-and 10-year survivals rates are both 87%. 3 However, patients with mucoepidermoid carcinomas can develop local or distant metastasis, which are typically unresponsive to conventional chemotherapy and radiation. In contrast, adenoid cystic carcinoma tends to present at a higher stage, is often unresectable, or, if resected, often has positive margins and subsequent local recurrences. The prognosis is also poorer with recent reported 5-and 10-year survivals of 55 and 39%, respectively. 3 As with mucoepidermoid carcinoma, the survival does not appear to be affected by traditional chemotherapy and radiation. Therefore, there appears to be a potential use for targeted novel therapies in the care of these patients.

Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas

“…In a recently published study, in two out of five (40%) of mucoepidermoid carcinoma of lung (which originate from minor salivary glands of the tracheobrochial tree), the L858R mutation was detected and all five patients well responded to TKI therapy independent of the mutation status . In contrast, in another study with 24 cases of adenoid cystic and mucoepidermoid salivary gland-type lung carcinomas, EGFR protein expression was found in 91%, but no mutation was detected in exons 18 -21 of the EGFR gene (Macarenco et al, 2008). In head-and-neck cancers, in which about 10% of cases showed responses to gefitinib, no mutations were noted in a US study, but 7% of tumours of Asian origin were found to harbour such mutations (Cohen et al, 2005;Lee et al, 2005).…”

Adenoid Cystic Carcinoma of the Lung with an <i>EGFR</i> Mutation

“…The authors found that one of 11 patients had EGFR mutations (13). In contrast, Macarenco and colleagues demonstrated that none of the 12 patients in their series had EGFR mutations in cases of adenoid cystic carcinoma (14). Moreover, Huo and colleagues reported that no EGFR mutations were detected in 24 cases of lung adenoid cystic carcinoma (15).…”

pEGFR-Tyr 845 expression as prognostic factors in oral squamous cell carcinoma

“…[31][32][33][34][35] Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year disease-free survival is still poor, despite the great scientific and financial efforts. For many years, the main prognostic factors of OSCC have been the conventional grading, staging and site of tumor.…”

“…For tissue microarray construction, areas of interest rich in non-necrotic tumoral cells were identified on corresponding haematoxylin and eosin-stained sections and marked on the source paraffin block. The source block was cored and a 0.6 mm core pEGFR-Tyr 845 proteins were determined by immunoblotting, 33 using anti pEGFR-Tyr 1068 and pEGFR-Tyr 845 antibodies. Representative cases of normal epithelia together with trisomic and amplified EGFR OSCC have been selected for this analysis.…”