Abstract

Background As the comprehensive genomic analysis of small cell lung cancer (SCLC) progresses, novel treatments for this disease need to be explored. With attention to the direct connection between the receptor tyrosine kinases (RTKs) of tumor cells and the pharmacological effects of specific inhibitors, we systematically assessed the RTK expressions of high-grade neuroendocrine carcinomas of the lung [HGNECs, including SCLC and large cell neuroendocrine carcinoma (LCNEC)].Patients and methodsFifty-one LCNEC and 61 SCLC patients who underwent surgical resection were enrolled in this research. As a control group, 202 patients with adenocarcinomas (ADCs) and 122 patients with squamous cell carcinomas (SQCCs) were also analyzed. All the tumors were stained with antibodies for 10 RTKs: c-Kit, EGFR, IGF1R, KDR, ERBB2, FGFR1, c-Met, ALK, RET, and ROS1.ResultsThe LCNEC and SCLC patients exhibited similar clinicopathological characteristics. The IHC scores for each RTK were almost equivalent between the LCNEC and SCLC groups, but they were significantly different from those of the ADC or SQCC groups. In particular, c-Kit was the only RTK that was remarkably expressed in both LCNECs and SCLCs. On the other hand, about 20 % of the HGNEC tumors exhibited strongly positive RTK expression, and this rate was similar to those for the ADC and SQCC tumors. Intriguingly, strongly positive RTKs were almost mutually exclusive in individual tumors.ConclusionsCompared with ADC or SQCC, LCNEC and SCLC had similar expression profiles for the major RTKs. The exclusive c-Kit positivity observed among HGNECs suggests that c-Kit might be a distinctive RTK in HGNEC.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-015-1989-z) contains supplementary material, which is available to authorized users.

Highlights

  • Large cell neuroendocrine carcinoma (LCNEC) is distinguished from small cell lung carcinoma (SCLC) based on its histological criteria, that is, a larger cell size, abundant cytoplasm, prominent nucleoli, vesicular nuclei or coarse chromatin, and a polygonal rather than a fusiform shape (Battafarano et al 2005)

  • C-Kit was the only receptor tyrosine kinases (RTKs) that was remarkably expressed in large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), compared with both ADC and squamous cell carcinomas (SQCCs)

  • C-Kit was the only RTK that was remarkably expressed in LCNEC and SCLC tumors, compared with both ADC and SQCC tumors

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Summary

Introduction

Large cell neuroendocrine carcinoma (LCNEC) is distinguished from small cell lung carcinoma (SCLC) based on its histological criteria, that is, a larger cell size, abundant cytoplasm, prominent nucleoli, vesicular nuclei or coarse chromatin, and a polygonal rather than a fusiform shape (Battafarano et al 2005). Despite these differences, LCNEC and SCLC share many similarities in terms of not. Electronic supplementary material The online version of this article (doi:10.1007/s00432-015-1989-z) contains supplementary material, which is available to authorized users.

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