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Ann Thorac Surg 2009;88:426-431. doi:10.1016/j.athoracsur.2009.04.038
© 2009 The Society of Thoracic Surgeons
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Original Articles: General Thoracic

Placenta Growth Factor Expression Has Prognostic Value in Malignant Pleural Mesothelioma

Eugenio Pompeo, MDa,*, Loredana Albonici, PhDb, Elena Doldo, PhDb, Augusto Orlandi, MDc, Vittorio Manzari, MD, PhDb, Andrea Modesti, MDb, Tommaso C. Mineo, MDa

a Department of Thoracic Surgery, Tor Vergata University, Rome, Italy
b Department of Experimental Medicine and Biochemical Sciences, Tor Vergata University, Rome, Italy
c Department of Anatomic Pathology, Tor Vergata University, Rome, Italy

Accepted for publication April 14, 2009.

* Address correspondence to Dr Pompeo, Department of Thoracic Surgery, Policlinico Tor Vergata University, V le Oxford 81, Rome, 00133, Italy (Email: pompeo{at}med.uniroma2.it).

Presented at the Poster Session of the Forty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 26–28, 2009.

Background: Malignant pleural mesothelioma is highly aggressive and recurs rapidly despite radical multimodality treatment. Progression of mesothelioma is thought to be governed by various growth factors, including vascular endothelial growth factor (VEGF). Placenta growth factor (PlGF) belongs to the VEGF family, although no study has yet investigated its expression in mesothelioma. We hypothesized that PlGF is overexpressed in mesothelioma and could have prognostic value in patients treated by extrapleural pneumonectomy.

Methods: We assessed by immunohistochemistry with semiquantitative classification (0 = no staining; 3 = strong staining), the expression levels of PlGF and its cognate receptors VEGF receptor 1, neuropilin-1, and neuropilin-2 in 27 patients with malignant pleural mesothelioma undergoing extrapleural pneumonectomy, in 14 patients with reactive mesothelium, and in 10 patients with normal mesothelium.

Results: Whereas PlGF was not expressed in normal mesothelium, it was overexpressed (grade 3) more frequently in mesothelioma than in reactive mesothelium specimens (11 or 41% versus 1 or 7%, respectively, p = 0.03). Furthermore, in mesothelioma, VEGF receptor 1 and neuropilin-1 and -2 were overexpressed in 18 specimens (67%), 8 specimens (30%), and 9 specimens (33%), respectively. Mean survival after extrapleural pneumonectomy was 17 months. An inverse relationship was found between the degree of PlGF expression and survival in months (R = –0.45, p = 0.01). No correlation was found between tumor stage and survival (R = –0.33) and between tumor stage and PlGF expression (R = 0.07).

Conclusions: We have shown that PlGF can be overexpressed in malignant pleural mesothelioma. In addition, the finding of an inverse relationship between PlGF expression levels and survival suggests a pivotal role of this factor in the recurrence and progression of mesothelioma after extrapleural pneumonectomy.




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