Abstract
The improvement in histological diagnostic tools, including neuroendocrine markers by immunohistochemistry (IHC), has led to increased recognition of non-small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little is known regarding the prevalence and clinical implications of NE feature in patients with NSCLC. In this study, we performed IHC in a tissue microarray containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of neuroendocrine marker with pathological and clinical features of NSCLC. The result showed that NE feature in NSCLC was detectable in almost 30% of studied patients, and tumors with NE feature were significantly correlated with pathological classification, clinical stages and cell differentiation of NSCLC. Our data also revealed that NE feature indicated worse overall survival and disease free survival. Compared with mutant p53, NE markers showed more significance as for prognostic evaluation. Multi-factor COX analysis further suggested a potential clinical impact for NE feature as an independent indicator of poor prognosis for NSCLC patients.
Highlights
Lung cancer remains one of the leading causes of cancer mortality worldwide [1, 2]
Because mutation of the p53 gene is one of the most significant molecular events occurring in about 50% of non-small cell lung cancer (NSCLC) and plays important roles in the tumorigenesis of lung epithelial cells and resistance to clinical treatments[13], we included IHC for p53 in this study and the positive immunostainings of mutant p53 was detected in 312 (69.2%) cases
We further found that the expressions of CD56 or SYN, or tumor with NE feature, were associated with TNM staging of NSCLC (p all < 0.05), and tumors at later staging had higher percentages of expressions for these molecular markers
Summary
Lung cancer remains one of the leading causes of cancer mortality worldwide [1, 2]. Primary carcinomas of the lung are traditionally classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). NSCLC constitutes approximately 85% of all primary lung cancers with adenocarcinoma, squamous cell carcinoma (SCC) and large cell carcinoma constituting the major histological types [7]. For patients with advanced stages of NSCLC when surgical excision is not an option, the adjuvant chemotherapy and radiotherapy has been extensively used[9]. Unlike small-cell lung cancer (SCLC) that often has neuroendocrine (NE) features, NSCLC is usually chemoresistant. Retrospective studies indicated that a subgroup of NSCLC patients with NE features may benefit from chemotherapeutic treatment. It is extremely important to be able to clarify this subgroup of NSCLC, and determine the clinical impacts of NE feature in NSCLC patients
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