Tissue inhibitor of metalloproteinase 2 (TIMP-2) expression in adenocarcinoma pleural effusions

Serous effusions are frequently a clinical manifestation of metastatic disease, with lung, breast and ovarian carcinoma and mesothelioma leading the list. The diagnosis of malignant effusion signifies disease progression and is associated with a worsening patient prognosis. The ability to grow in a dense exudative fluid suggests that the malignant cells are capable of acquiring nutrients, surviving and proliferating, despite the lack of a solid-phase scaffold. During proliferation, neoplastic cells release ligands and matrix metalloproteinases (MMPs) into their environment, which dissolve the extracellular matrix (ECM). Tissue inhibitors of metalloproteinase (TIMPs) are endogenous regulators of MMPs, the principal enzymes responsible for the degradation of ECM in metastasis, and reduce their proteolytic activity. TIMP-2 has demonstrated an association between high tumor tissue expression levels and poor prognosis. The purpose of this preliminary study is to investigate, by immunocytochemistry, TIMP-2 expression in non-neoplastic and metastatic adenocarcinoma pleural effusions. We selected 16 cases of reactive mesothelio, 7 of normal mesothelio, 14 of lung adenocarcinoma, 9 from the ovary, 4 from the gastrointestinal tract and 3 from the breast. In 23/30 cases (76%), we detected adenocarcinoma cells with strong TIMP-2 expression. Positive TIMP-2 expression was found in 2/7 cases (28%) of normal and 2/16 (12%) of reactive mesothelio. A statistical association was detected between TIMP-2 expression and metastatic adenocarcinoma cells compared to reactive and normal mesothelial cells (p<0.00003). The calculated sensitivities for TIMP-2 compared to CEA and Ber-EP4 were, respectively, 76.7, 80.0 and 93.3%, and the specificities 82.6, 95.7 and 87.0%. In conclusion, immunocytochemical detection of TIMP-2 could be considered an interesting marker in metastatic adenocarcinoma pleural effusions, and could possibly be used as a component of an antibody panel in diagnostic cytopathology.