Nuclear Localization of Crabp1 in Neuroendocrine Lung Tumors Is Associated With the Degree of Tumor Malignancy

Abstract

Bronchopulmonary neuroendocrine tumors (NETs) refer to malignant epithelial neoplasms of neuroendocrine origin, which form highly heterogeneous group with respect to biological behavior and clinical manifestations. Three main categories of different grades of malignancy are distinguished in the diagnosis of lung NETs: typical carcinoids (TK), atypical carcinoids (AK) and the most aggressive low-differentiated tumors including small-cell and large-cell neuroendocrine lung carcinomas. These groups differ in terms of disease prognosis and therapeutic approaches, but the criteria currently used do not always allow clear boundaries between different histological variants. The search for additional diagnostic parameters and individual prognosis markers is currently actual for the grading and optimal classification of NETs. For the first time we studied the expression of Retinoic Acid Binding Protein-1 (CRABP1) in different variants of lung NETs. IHC analysis of 43 samples of lung NETs with various degrees of differentiation and grades revealed the statistically significant correlation between nuclear localization of CRABP1 and proliferation index «Ki-67» and tumor grade. The results pointed on the involvement of CRABP1 in the pathogenesis of lung NETs and indicated the need for further investigation of the relationship of the nuclear CRABP1 with clinical parameters and patient survival to determine whether this protein can be used as a marker for differential diagnosis and/or disease prognosis.