VEGF-D as a marker in the aid of malignant metastatic pleural effusion diagnosis.
BACKGROUND
The sensitivity in cytology diagnosis of malignant metastatic pleural effusion (MMPE) is insufficient nowadays due to the similarity of the reactive mesothelial cells and malignant cells. Vascular endothelial growth factor (VEGF) is one of the key factors in tumor lymphangiogenesis and metastasis. Therefore, the aim of this study was to evaluate the value of VEGF and its homologs in the aid of MMPE diagnosis.


METHODS
A total of 217 pleural effusions samples were eligible for analysis. Among them, 81 malignant and 22 benign cases were made into the cell blocks for the immunocytochemical (ICC) staining of VEGF-A, VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3 expression. Another 114 samples (41 malignant and 73 benign cases) were subjected to the ELISA test for the protein level of VEGF-D.


RESULTS
In a total of 156 MMPE, only VEGF-D expression by ICC stain was significantly different between malignant (92.6%) and benign cases (9.1%) with P<0.001 in either nuclear or cytoplasmic staining. Only 6 malignant cases showed negative stain results. In addition, 3 of the 4 lung small cell carcinoma were immunoreactive for VEGF-D. However, some lymphocytes also showed nuclear staining pattern of VEGF-D. In contrast, the ELISA test for the VEGF-D protein levels failed to demonstrate the difference between malignant and benign pleural effusions.


CONCLUSIONS
Among VEGF homologs, MMPE from various kinds of tumor origin, VEGF-D showed 92.6% rate of positive expression. ICC stain of VEGF-D is a useful marker in the aid of MMPE diagnosis.