Kinases and their inhibitors, phosphatases, are key regulators of several cellular functions, and their appropriate learn more activity is required for the cellular homeostasis; on the contrary, their aberrant activation is crucial in driving oncogenesis. The concept that cancer-mutated kinases molecularly mark “druggable” targets has resulted in intensive efforts to

survey the kinome across a wide spectrum of human tumor types for mutations and to the development of several targeted inhibitors [3]. On this basis, we reasoned that, as in malignant proliferations, TK activation could play a role in IPF, although few data about molecular mechanisms involved in disease onset and progression are available. A confirmation of a role of TK activation

pathways in IPF would make them actionable with specific molecules, in a similar fashion to cancer-targeted therapy. We selected and analyzed 17 consecutive IPF samples derived from medical thoracoscopy cases from a cohort of patients aged ≥ 18 years who referred to our Institution for diagnosis and therapy. In all patients with IPF, the histopathologic examination revealed all of the major features of usual interstitial selleckchem pneumonia (UIP ) [temporally and architecturally heterogeneous interstitial fibrosis, with fibroblast foci (FF), microscopic honeycombing, subpleural and periseptal accentuation, and absence of histologic features specific of other diseases], which is a prerequisite for the diagnosis

of IPF. The final diagnosis of IPF was based on the diagnostic criteria of the American Thoracic Society/European Respiratory Society Consensus Classification System after evaluation of all clinical, laboratory, and instrumental data [4] and [5]. We also checked 40 non–small cell lung cancer (NSCLC) samples [20 adenocarcinoma (ADC) and 20 from squamous cell cancer] obtained through endobronchial, transbronchial, or transthoracic biopsy. Clinical characteristics of cases analyzed are reported in Table 1. Orotidine 5′-phosphate decarboxylase Immunohistochemical (IHC) analysis was performed with antibodies against phospho–mammalian target of rapamycin (P-mTOR) (1:100, rabbit monoclonal, clone 49 F9; Cell Signaling Technology, Danvers, MA), phosphatase and tensin homolog (PTEN) (1:400, mouse monoclonal, clone 6H2.1; Dako, Cernusco sul Naviglio, MI, Italy), phospho-MET (P-met) (1:100, rabbit monoclonal, clone D26; Cell Signaling Technology), and phospho-ezrin/radixin/moesin (P-ERM) (1:300, rabbit monoclonal, clone 41A3; Cell Signaling Technology) on 4-μm–thick paraffin sections. Tissue sections were incubated at 60°C overnight and then deparaffinized. The slides underwent 40 minutes of heat-mediated antigen retrieval in citrate buffer (pH 6) and incubated for 20 minutes with ready-to-use normal horse blocking serum. Primary antibody was incubated overnight at + 4°C.