Abstract 5301: Blood vessel structure and expression of permeability related factors in advanced lung cancer complicated with pleural effusion
Authors: Damianovich Maya , Siloni Goni Hout , Barshack Iris. , Simansky David , Kidron Dvora , Onn Amir 
Published: August 2012

Abstract
Background. Malignant pleural effusion (MPE) is a common and debilitating condition in patients with lung cancer. For unknown reasons, some tumors are more strongly associated with the condition than others. The pathophysiology of this condition has not been fully determined and to date no specific medical treatment is available. Our goal was to study the structure and assess the permeability related factors in MPE associated blood vessels to better understand the mechanisms of this condition. Methods. Immunohistochemical analysis of human NSCLC formalin-fixed paraffin-embedded specimens from patients who underwent lobectomy (MPE- cases) or pleural biopsy (MPE+ cases) was employed. Nine adenocarcinomas (AC) and eight squamous cell carcinomas (SCC) with and without MPE were studied. For endothelial cell (EC) staining and microvessel density (MVD) determination, the anti-CD31 Abs was employed. Pericytes were stained by aSMA Abs. Coexpression of some of receptor tyrosine kinases (PDGFR, VEGF/VEGFR, Tie-2) was also evaluated. Results. In SCC complicated with MPE a narrow, clogged and fibrotic vessels were seen in tumors located near the pleura (pleura involved). In MPE positive AC specimens there were regions of tumor vessels where ECs were irregularly laminated and hardly noticed. This observation was also confirmed by CD31 staining where lower number of positive vessels related to the total number of vessels was observed (88.4% in MPE+ vs. 94.8% in MPE- cases, p&lt;0.05). Regarding the vessel coverage by pericytes, the pericyte expression (aSMA staining) was shown to be less extensive in cases with than without effusion (59.1% vs 96.2%, p&lt;0.001) probably because of their thinning or even detachment. This clarification could also explain the finding that the PDGFR was more expressed on ECs on MPE - tumors than on MPE + ones. For VEGF and VEGFR staining, the staining index was more prominent in tumors with than without effusion, for both staining area and staining intensity (1.7 and 1.9, respectively). However, in distinction to the staining of tumor cells almost no vessel EC staining by VEGFR Abs was seen, while staining by anti-VEGF Abs was substantial. Similarly, the staining of Ang-2 receptor (Tie-2) was found in the cytoplasm of the tumor cells, but not in the vascular endothelium, regardless the pleura effusion positive or negative features. Conclusions. To our knowledge this is one of the first studies on structural abnormalities of blood vessels in human lung cancer malignant pleural effusion. For now, because of the relatively small number of cases analyzed no single mechanism was found able to explain the occurrence of a pleural effusion, and it is likely that multiple factors contribute to effusion formation. This formulation may also better explain why some patients with pleural metastases have malignant effusions while others do not.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5301. doi:1538-7445.AM2012-5301