TOP2A expression as the essential prognostic factor in lung neuroendocrine tumors

Abstract

Lung neuroendocrine tumors (NETs) are considered rare, but their incidence increasing worldwide. According to recent studies, NETs take up to 25% of all lung malignancies. Bronchopulmonary NETs are heterogeneous neoplasms classified into four histological types: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell lung carcinoma. Often lung NETs are clinically silent or cause non-specific symptoms; the correct diagnosis usually is delayed. Regional and distant metastasis turn out to be the first manifestation of the disease in more than 40% of patients, which has critically negative effect on the survival. Morphology and immunohistochemistry (IHC) are important in lung NETs diagnosis, but IHC results remains ambiguous in some cases. Ki-67 helps to distinguish carcinoids from high-grade lung NETs, but is not reliable enough to determine the disease clinical course and prognosis. The aim of this study was to evaluate expression of proliferative marker TOP2A as a prognostic criterion for lung NETs. Methods. Surgical and biopsy material from 50 patients with lung NETs before chemotherapy prescribing was used for this study. Regular morphological examination and IHC was performed in each case. Non-parametric statistics was used for Ki-67 and TOP2A expression evaluation. Results. Higher Ki-67 scores corresponded to TOP2A higher expression (Spearman’s correlation, r=0.603, p=0.00000362). There was no significant association of Ki-67 and necrosis severity, and metastases. At the same time TOP2A expression related to several key features of lung NETs. TOP2A rates were significantly linked with necrosis severity and metastasis in lymph nodes. Low TOP2A scores were associated with longer overall survival (OS); a cutoff TOP2A ≤13% was critical for patients’ OS. Conclusions. TOP2A appeared to be more reliable than Ki-67 and can be used as the additional predictor for regional metastatic lesions at the time of diagnosis and for shorter survival rates in patients with lung NETs. But further prospective studies are desirable to clarify the «critical rates» of TOP2A as a prognostic factor at bronchopulmonary NETs.