Morphological and immunohistochemical prognostic criteria for small cell lung cancers

Abstract

Background. Despite the fact that a lot of information on molecular genetic changes in lung cancers has been accumulated, there is still a knowledge gap regarding determination of the key factors of oncogenesis and trigger factors that cause metastasis and progression of small cell lung cancer (SCLC). The problem of comprehensive assessment of prognostic importance of molecular genetic changes, a range of IHC markers that are used for diagnosing and prognosing SCLC, and impact of the epithelial-mesenchymal transformation (EMT) processes on the risk of development of the tumor process and lethal outcome of the disease remains relevant. Purpose – to improve morphological prognostic criteria for the course of SCLC based on the research of clinical morphological and molecular biological characteristics of primary tumors with different clinical behavior and prognosis. Materials and methods. The material of the research was autopsy data and surgically removed tumors in hospitals in Kharkiv. We formed two groups based on the type of SCLC (limited-stage (LSCLC) and extensive-stage (ESCLC)) and overall survival (OS) of patients. IHC studies were performed using the following markers: CD56, CD117, Ki-67, pan-cytokeratin, E-cadherin, vimentin, N-cadherin, and CD44. We took into account EMT stage with determination of coexpression of the epithelial (pan-cytokeratin and E-cadherin) and mesenchymal (vimentin and N-cadherin) markers. Results. We have found that poor prognostic criteria should include: emergence of vimentin expression in cancer cells, increased expression level of N-cadherin, presence of EMT and stage 3+ EMT (stages 3–5). High levels of E-cadherin and Ki-67 expression are favorable prognostic criteria. Some factors such as clinical morphological features, data of the histological study, expression of pan-cytokeratin, CD44, and markers of the neuroendocrine phenotype have limited prognostic value. Conclusions. We have identified prognostic criteria for SCLC regarding overall survival and belonging to the stage of limited or extensive process. The recommended panel of the IHC markers should include: Ki-67, E-cadherin, N-cadherin, vimentin, pan-cytokeratin, taking into account the stage of EMT.