Structural basis for hyperpermeability of tumor vessels in advanced lung adenocarcinoma complicated by pleural effusion.
BACKGROUND
Malignant pleural effusion (MPE) has a profound impact on quality of life and survival in patients with lung cancer. Identification of the factors within the tumor and its environment that mediate MPE is still lacking.


METHODS
Intratumoral microvessel density (MVD), endothelial cell and pericyte (PC) capillary coverage, endothelial cell (EC)-PC relationship, lymphatic endothelium integrity, and the expression of receptor tyrosine kinases were all assessed immunohistochemically in pleural tumor biopsy specimens from 24 patients with lung adenocarcinoma (ADC) with and without pleural disease, with the aim to evaluate the involvement with MPE.


RESULTS
In the effusion-positive⁺ specimens, MVD values were found to be significantly higher, and a number of vessels were noted to lack immunoreactivity for ECs (CD31). Likewise, PC α-smooth muscle actin (αSMA) expression was also less extensive in the MPE⁺ cases. The observation of only sporadic staining of PCs can also explain the findings regarding platelet-derived growth factor receptors (PDGFRs), the expression of which, although more prominent in MPE⁺ samples, were almost exclusively detected on tumor stromal cells and not on vascular PCs. Conversely, vascular endothelial growth factor receptors (VEGFRs) appeared on both kinds of cells. With respect to lymphatic vessels, lymphatic intraluminal tumor cells were occasionally found in MPE⁺ specimens.


CONCLUSIONS
Our study suggests that disturbed vessel wall integrity, as well as abnormalities of fluid clearance by the lymphatic system, together with overexpression of growth factors, may take part in the pleural fluid accumulation in lung ADCs. Results of the decreased PC capillary coverage and PDGFR expression in MPE are discussed.
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel. Electronic address: Maya.Damianovich@sheba.health.gov.il.
Maya
M
Damianovich
Goni
G
Hout Siloni
Iris
I
Barshack
David A
DA
Simansky
Debora
D
Kidron
Erel
E
Dar
Camila
C
Avivi
Amir
A
Onn
D000230:Adenocarcinoma / Q000098:blood supply* / Q000150:complications; D002196:Capillaries / Q000473:pathology*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000150:complications; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D020286:Pericytes / Q000473:pathology; D010996:Pleural Effusion / Q000209:etiology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D020797:Receptor, Platelet-Derived Growth Factor beta; D040281:Vascular Endothelial Growth Factor Receptor-1
Human lung adenocarcinoma; immunohistochemistry; malignant pleural effusion; pleural biopsy