Unique p53 and epidermal growth factor receptor gene mutation status in 46 pulmonary lymphoepithelioma‐like carcinomas

Abstract

p53 and epidermal growth factor receptor (EGFR) are common genes involved in the pathogenesis of lung cancer, but their roles in lymphoepithelioma-like carcinomas (LELC) are unclear. In this study, we investigate the roles of p53 and EGFR in LELC carcinogenesis. Forty-six pulmonary LELCs were identified to evaluate p53 and EGFR aberrations. p53 mutations were identified in three patients, which all occurred in exon 8. EGFR mutations were detected in 8 of 46 cases with a majority of exon 21 mutations but without L858R. The other cases harbored mutations in exons 20 and 18. Only one case gained a deletion in exon 19. Notably, EGFR mutation was more commonly observed in patients with tumor size £3 cm (P = 0.014). In addition, there was a trend of more common EGFR overexpression in female (22 ⁄ 30) than in male patients (7 ⁄ 16, P = 0.061). However, there was no correlation between p53 ⁄ EGFR mutations and protein expressions, suggesting the presence of complex mechanisms. p53 and EGFR mutations are uncommon in LELCs, indicating that these genes are not the important events in carcinogenesis for this tumor subtype. The EGFR mutation in 35% patients with LELC tumors <3 cm in size suggests the potential benefits to EGFR tyrosine kinase inhibitors of inoperable LELCs. (Cancer Sci 2011; 102: 282-287) T he majority of tumors have evidence of mutational inactivation of tumor suppressor genes and activation of oncogenes. Mutation of one p53 allele and loss of the normal p53 allele occur in many tumors including lung cancers. These alterations apparently contribute to the development of cancer by interfering with the tumor suppressor activity of p53. In addition, overexpression of mutant p53 may cause cellular transformation, whereas transfection and expression of a normal p53 gene in cells having a mutated p53 can suppress cellular transformation and inhibit cell proliferation.(1) It has been reported that somatic mutations and increased expression of p53 are frequently found in approximately 23% and 65% of non-small-cell lung cancer (NSCLC), respectively. Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is involved in promoting cell division, migration and angiogenesis, and inhibiting apoptosis.(5) Loss of control of EGFR because of deregulation, amplification, or mutations may result in malignant change of cells.(6) Gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE, USA), an inhibitor of EGFR tyrosine kinase, has a novel antitumor effect on NSCLC. The better treatment outcomes of tyrosine kinase inhibitor in NSCLC patients are strongly associated with mutations at the EGFR tyrosine kinase domain (exons 18-21) in EGFR of tumor tissues. (7,8) Depending on the tumor subtypes and different ethnicity, Caucasian NSCLC patients have an EGFR mutation frequency of <10% compared with a mutation rate of at least 30% in East Asian patients. (2,9,10) Lymphoepithelioma-like carcinoma of the lung (LELC) was first reported in 1987.(11) It is a rare form of NSCLC predominantly affecting young non-smoking Asi...

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

“…More peculiar was the finding that P53 (+) in primary pulmonary LELC showed a favorable DFS in our analysis. This tendency was also observed by Chang et al in three primary pulmonary LELC patients with P53 gene mutations, which is completely opposite from results in other subtypes of NSCLC (15,16,20). To our knowledge, this is the first report concerning the prognostic significance of P53 expression in LELC of the lung.…”

“…Similarly, P53 mutations were shown to be the most common mutation in primary pulmonary LELC by Dr. Hong SD from our center. This result was chosen as a poster board display during the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), but this finding was inconsistent with a study by Chang et al (20). In this study, P53 status was evaluated using IHC, since the expressed mutant P53 protein, which had been shown to have a longer half-life than wild-type P53 protein, could accumulate at the nuclear membrane and be detected by IHC.…”

Primary lymphoepithelioma-like carcinoma of the lung in an adolescent girl with unusual presentations

“…[4][5][6][7] It occurs mostly in the middle age without any definite sex predilection. 5 In contrast to the non small cell carcinomas of the lung, primary LELC has been found to have minimal association with cigarette smoking.…”

“…Most of the symptomatic patients presented with complaints like cough, chest pain or haemoptysis. [4][5][6][7] It usually forms unilateral, solitary sub-pleural nodule without affecting major bronchi. However, some cases with bilateral extensive disease at the time of presentation have also been described.…”

“…3 Our knowledge about the tumour is mostly derived from three large cohorts from south-east Asia. [4][5][6][7] We report this rare case in a 14-year-old girl who presented with unusual symptoms.…”