Mutation status of epidermal growth factor receptor and clinical features of patients with combined small cell lung cancer who received surgical treatment

Abstract

Abstract. The mutation status of epidermal growth factor receptor (EGFR) is correlated with the response of tumors to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), suggesting its usefulness as a biomarker in NSCLC. The incidence of EGFR mutation in NSCLC is higher in China than in the United States and European countries. There have been some case reports concerning cases of gefitinib-responsive small cell lung cancer (SCLC) with EGFR mutations. However, few large studies concerning the mutation status of SCLC patients have been performed. We detected EGFR mutations in exons 19 and 21 of 40 SCLC patients, three of whom had combined SCLC, from the Zhejiang Cancer Hospital using xTAG technology. Only two patients with combined SCLC had an EGFR mutation in exon 19. To determine the EGFR mutation status and clinical features of combined SCLC, we retrospectively analyzed the clinical features of seven patients with combined SCLC who had undergone surgical treatment in Zhejiang Cancer Hospital between 2007 and 2010. EGFR mutations in exons 19 and 21 were detected using the pyrosequencing assay. Of the seven patients with combined SCLCs, 71.4% were male, 71.4% were heavy smokers, most were over 60 years old and 71.4% of the cases were combined adenocarcinoma. Chemotherapy treatment and tumor stage were correlated with survival time. Of the seven cases, one had a mutation in exon 19 of EGFR in both the conventional SCLC and SCLC combined adenocarcinoma components. Combined SCLC commonly occurs in patients who are heavy smokers, male and over 60 years old, and most of the combined type cases are adenocarcinoma. The treatment of combined SCLC may be applied to cases of conventional SCLC. EGFR mutations may therefore occur in combined SCLCs, especially in SCLC combined adenocarcinoma in China. IntroductionAn epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be used as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (1-5). The results of the INTEREST trial (6) suggest that gefitinib is able to provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers, including mutation status, may additionally identify which patients are likely to gain greatest progression-free survival (PFS) and overall response rate (ORR) benefit from treatment with gefitinib. Two hot spots of EGFR mutations are in-frame deletion at codons 747-749 (DEL) in exon 19 and a missense mutation at codon 858 (L858R) in exon 21. A case study concerning a Japanese patient with gefitinib-responsive small cell lung cancer (SCLC) reported that the patient had a deletion in exon 19 of EGFR (7). Another case study has reported that an American SCLC patient who had never smoked and who had an EGFR mutation responded to gefitinib (8). In China, there has also been a case report of a patient with SCLC who responded to gefitinib, but the status of the mutation is unknown (9). Therefore, the EGFR mutation ...

Synchronous Primary Lung Cancer Presenting with Small Cell Carcinoma and Adenocarcinoma

“…In addition, we list five reports which described the EGFR mutation status in resected specimens with combinations of SCLC and adenocarcinoma. [7][8][9][10][11] Fifteen patients were extracted. They also had received no chemotherapy, target therapy, or radiation therapy prior to surgery.…”

Usefulness of carcinoembryonic antigen in the diagnosis of small cell lung cancer combined with adenocarcinoma

“…Few studies have investigated C-SCLC, and more research should be conducted to identify the clinical features of these patients. 13 Some studies have indicated that the clinical characteristics of C-SCLC patients do not significantly differ from those of pure SCLC patients. 6,8,14 Consistent with this, we found no significant differences in the clinical characteristics between SCLC and C-SCLC patients.…”

“…6 Our previous study has shown that epidermal growth factor receptor (EGFR) mutations may occur in C-SCLC, particularly when the "combined" component is adenocarcinoma. 13 More effective treatments (e.g., EGFR-tyrosine kinaseinhibitors) can be administered to patients who have SCLC combined with adenocarcinoma if a definite diagnosis is achieved.…”

PIK3CA Mutations in Resected Small Cell Lung Cancer

“…A phase-2 trial of gefitinib in patients with chemosensi tive and chemorefractory relapsed SCLC failed to show any benefit from the use of gefitinib [8]. The EG-FR mutation is rare in SCLC and mainly occurs in combined SCLC or female non-smoker patients [9][10][11][12][13]. A phase-2 trial of imatinib (ST1571) in relapsed SCLC patients with expression of the c-kit gene reported negative results [13].…”

“…The EG-FR mutation is rare in SCLC and mainly occurs in combined SCLC or female non-smoker patients [9][10][11][12][13]. A phase-2 trial of imatinib (ST1571) in relapsed SCLC patients with expression of the c-kit gene reported negative results [13]. A pyrosequencing assay was used to detect mutations in c-kit exons 9 and 11 in 36 SCLC patients who underwent surgical treatment at the Zhejiang Cancer Hospital, Hangzhou, China, between 1998 and 2010; no mutations in c-kit exons 9 and 11 were detected [15].…”