Abstract
Abstract Background: GP88 (progranulin) is a growth and survival factor implicated in tumorigenesis and drug resistance for various cancers. GP88 tissue expression measured by IHC is inversely correlated with survival. We now evaluate GP88 tissue lung cancer small cell carcinoma (SCLC), non-small cell lung carcinoma (NSCLC) and mesothelioma. Methods: GP88 expression was determined by immunohistochemistry on tissue sections from normal lung, pleura, benign mesothelial proliferation, SCLC, NSCLC and mesothelioma. In the case of NSCLC, GP88 expression in tumor tissues from patients with localized (stage I-II) and locally advanced disease (IIIa-IIIb) was determined and correlated with clinical outcome disease-free survival (DFS) and overall survival (OS). Serum GP88 levels from patients with metastatic NSCLC was quantified by EIA and compared to GP88 levels from patients with COPD and from healthy individuals. Results: GP88 was significantly expressed in NSCLC (adenocarcinoma and squamous cell) and mesothelioma (epitheloid, sarcomatoid and biphasic subtypes) tumors. In contrast, normal lung tissue, benign lung disease, pleura, benign mesothelial proliferations and SCLC were negative. There was a significant increased risk of recurrence and death for patients with resected NSCLC (stage I,II) with high expression (GP88 IHC score 3+) compared to patients with GP88IHC score <3+, with HR = 2.28 (p = 0.0076) for DFS and HR = 2.17 (p = 0.014) for OS In locally advanced disease progression-free survival after chemoradiotherapy was inferior (HR = 2.9, p = 0.022) for GP88 scores of 3+ vs. <3+ In addition, patients with stage IIIb/IV NSCLC had a significantly elevated serum GP88 when compared to control subjects (49.9ng/ml vs. 28.4ng/ml, p<0.0001). 67% of mesothelioma tumors (stage I-III) scored positive for GP88 with 23% of tissue examined showing a GP88 score of 3+. Conclusions: This is the first study investigating GP88 expression in various thoracic malignancies. Differences of GP88 expression were observed in different lung tumor types with NSCLC and mesothelioma being positive. Correlation with clinical outcomes in NSCLC demonstrates that measuring the GP88/Progranulin IHC tumor tissue expression using the anti-GP88/PGRN 6B3 antibody provides information on the risk of recurrence and death of patients with stages I-III NSCLC and that serum GP88 levels are elevated in advanced disease. Future research will focus on investigating the prognostic potential of GP88 tissue expression and serum levels for mesothelioma patients. Citation Format: Ginette Serrero, Martin J. Edelman, Pablo Bejarano, Douglas M. Hawkins, David Hicks, David N. Reisman, Olga Ioffe, Josephine Feliciano, Binbin Yue. Progranulin (GP88) expression in thoracic maligancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4339. doi:10.1158/1538-7445.AM2015-4339
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