EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: Implications for anti‐EGFR treatment of a rare lung malignancy

Abstract

Sarcomatoid carcinomas (SC) of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous cell components and characterized by a more aggressive outcome than other histological subtypes of nonsmall cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR)‐targeted therapies have emerged as a promising therapeutic approach in patients with advanced typical NSCLC such as adenocarcinoma, the potential clinical activity of these drugs in lung SC is still unknown. To investigate this point, we have analyzed the status of 4 EGFR pathways biomarkers in a series of lung SC. EGFR protein expression, EGFR gene copy number, EGFR mutational status and KRAS mutational status were assessed in a series of 22 consecutive cases of primary lung SC. EGFR protein overexpression was observed in all the cases. High level of polysomy (≥4 copies of the gene in >40% of cells) was detected in 5 cases (23%). No EGFR mutation was detected. KRAS mutations were found in 8 patients (38%; Gly12Cys in 6 cases and Gly12Val in 2 cases). The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC. The rare incidence of increased EGFR gene copy number, the lack of EGFR mutation and the high rate of KRAS mutation observed in our series also suggest that most patients with lung SC are not likely to benefit from anti‐EGFR therapies. © 2009 UICC

Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: Comparison of sarcomatous and carcinomatous areas

“…In our patients with pulmonary PC, the male or smoker predominance was similar to previous reports [ [4][5][6]. Only a single study has previously addressed PD-L1 expression in pulmonary SCs, and it demonstrated that PD-L1 was frequently expressed in up to 69.2% of cases [14].…”

“…Of these, PCs, accounting for the majority of pulmonary SCs, show highly aggressive biological behaviour and resistance to chemotherapy and radiotherapy [1][2][3][4]. Meanwhile, genetic alterations eligible for molecular targeted therapies are rarely in pulmonary PC [5,6], thus demanding development of a novel therapeutic strategy.…”

Clinicopathologic Outcomes of Curative Resection for Sarcomatoid Carcinoma of the Lung

“…However, both neoadjuvant and adjuvant treatment showed no significant influence on survival or recurrence. Until now, innovative treatments such as monoclonal antibodies that target epidermal growth factor receptor mutations have shown no definitive effect on the outcome [21,22,23]. …”

Primary adrenal sarcomatoid carcinoma metastatic to the lung: Case report and review of the literature

“…Molecularly-targeted tumor therapy has previously been studied with findings indicating that certain oncogenes, growth factors and tumor-suppressor genes are associated with adrenocortical carcinoma tumorigenesis. It should be noted that epidermal growth factor receptor (EGFR) is overexpressed in the majority of adrenocortical carcinomas (34), and has been demonstrated to have a significant role in sarcomatoid carcinomas (35,36). Anti-EGFR therapy may comprise a feasible approach for the improvement of prognosis in patients with adrenal sarcomatoid carcinomas.…”