Low frequency of mutation of epidermal growth factor receptor (EGFR) and arrangement of anaplastic lymphoma kinase (ALK) in primary pulmonary lymphoepithelioma‐like carcinoma

Abstract

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated. Method: We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from based on their mention of "driver mutations" and "the response of TKIs to mutant PLELC". Results: Genetic alterations of EGFR/ALK were tested in 203 patients (203/330, 61.5%). Five patients (5/175, 2.9%) had EGFR mutation and three patients (3/140, 2.1%) had ALK alteration. From the total of 15 articles identified from electronic searches, 1071 PLELC cases mentioned the driver mutations. EGFR mutation and ALK rearrangement were detected in 15 patients and one patient, respectively. In total, there were four EGFR/ALK mutant PLELC patients who received targeted therapy as palliative treatment at the GLCI and in the literature. However, there was disease progression in all cases one month after use of TKIs. Conclusion: The mutation rates of EGFR and ALK were low in PLELC. EGFR and ALK TKIs showed limited response in EGFR/ALK mutant PLELC. Further studies are needed to explore other molecular targets to optimize the therapeutic strategy for PLELC. Key points• The mutation rates of EGFR and ALK in PLELC were lower than other common types of non-small cell lung cancer. • EGFR/ALK TKIs showed a limited response in EGFR/ALK mutant PLELC.• This large cohort study demonstrates the prevalence of EGFR mutation and ALK alteration, and summarizes the response of targeted therapy in mutant PLELC patients.

The clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma: A systematic review and meta-analysis

“…Besides, the relationship between PD-L1 expression and gene mutations of lung was also arouse concern in recent studies [25,44,45]. Unlike other NSCLC subtypes, PPLELC patients showed lower mutation rates of some common gene, such as ALK, KRAS and EGFR [25,44,45]. The explanation for this may be that there had a unique gene profile in LELC of lung [45].…”

“…Unlike other NSCLC subtypes, PPLELC patients showed lower mutation rates of some common gene, such as ALK, KRAS and EGFR [25,44,45]. The explanation for this may be that there had a unique gene profile in LELC of lung [45]. Recently, Xie et al [44] recruited 29 PPLELC patients in China to explore the genomic landscape.…”

Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing

“…The primary treatment of pulmonary LELC is radical resection at an early stage and multimodal therapy, including chemotherapy and radiotherapy, at an advanced stage [ 5 ]. Previous molecular studies have shown that major driver events, i.e., EGFR , KRAS , MET , ALK and ROS1 , are rare in pulmonary LELC [ 5 , 6 , 7 , 8 , 9 , 10 ]. Therefore, pulmonary LELC patients may not benefit from personalized targeted therapies commonly used for NSCLC.…”

Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice

“…It is of interest to highlight that for non-adenocarcinoma lung tumors, notably for squamous cell carcinoma, but also for other rare histological subtypes such as pulmonary lymphoepithelioma-like carcinoma, the detection of an ALK rearrangement is not mandatory with tissue biopsies [ 1 ]. However, though uncommon these tumors can present an ALK rearrangement [ 3 , 4 , 5 , 6 , 7 , 8 ]. Moreover, these rare tumors showed response to first- and second-generation ALK-TKI [ 6 , 99 , 100 ].…”

“…ALK rearrangements are found in 3–5% of patients with NSCLC [ 2 ]. Interestingly, ALK rearrangements occur mainly in adenocarcinoma, but though rare can be detected in other histological subtypes of lung cancers such as squamous cell carcinoma and rarely in pulmonary lymphoepithelioma-like carcinoma [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. The detection of an ALK rearrangement of a patient with advanced stage NSCLC is performed with a tissue sample by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), targeted polymerase chain reaction (PCR) or next-generation sequencing (NGS) [ 9 , 10 ].…”