The Clinical Significance of mTOR, ZEB-1, ROCK1 Expression in Lung Tissues of Idiopathic Pulmonary Fibrosis

Abstract

Abstract SESSION TYPE: New Insights into Idiopathic Pulmonary FibrosisPRESENTED ON: Sunday, October 21, 2012 at 01:15 PM - 02:45 PMPURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, and usually lethal lung disease of unknown cause. There is a report that mTOR (mammalian target of rapamycin) inhibitor, rapamycin, inhibit pulmonary fibrosis in animal model. ZEB-1(Zinc finger E-box-binding homeobox 1), participate in epithelial-mesenchymal transition and ROCK1 (Rho-associated, coiled-coil containing protein kinase 1), contributing to actin stability may have a role in pulmonary fibrosis. This study was performed to identify the clinical significance of mTOR, ZEB-1 and ROCK1 expression in IPF patients.METHODS: The expression of mTOR, ZEB-1 and ROCK1 were evaluated by immunohistochemical method in 30 surgically resected lung tissues of IPF patients. Expression of mTOR, ZEB-1 and ROCK1 were scored using both the intensity of staining and the percentage of positive stained alveolar cells. These results were correlated with other clinicopathologic features.RESULTS: Median age was 57 (38-74) and 14 patients were male (46.7%). During the median 40 (5-74) months of follow-up period, 24 (80%) patients survived. The mTOR expression score was significantly correlated with fibrotic score (r=0.441, p=0.015) In mTOR positive group (n=26), radiologic honeycombing and histologic fibrosis score was higher (palt;0.01) than mTOR negative group (n=4). ZEB-1 positive group (n=26) showed higher histologic fibrosis score (p=0.005) than negative group (n=4). All the patients with mTOR or ZEB-1 negative group were survived, compared to non-survived patients in mTOR or ZEB-1 positive group. However, ROCK1 expression was not associated with other clinicopathologic features.CONCLUSIONS: The expression of mTOR and ZEB-1 in IPF patients significantly correlates with fibrosis score. Patients without expression of mTOR or ZEB1 were all survived during the follow up period.CLINICAL IMPLICATIONS: The mTOR and ZEB-1 may have a role in the pathogenesis and progression of IPF.DISCLOSURE: The following authors have nothing to disclose: Young Whan Kim, Jomg Sun Park, Hyo Jin Park, YoungSik Park, Sang-Min Lee, Hae-Joon Yim, Chul-Gyu Yoo, Sung Koo HanNo Product/Research Disclosure InformationSeoul National University Hospital, Seoul, Republic of Korea.