title: Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.
abstract: A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) and without (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-β), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E-cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-β, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. N-cadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC.
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.affiliation: Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Olson
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Clawson
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bruggeman
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Varlotto
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA.
authors.forename: Dani S
authors.initials: DS
authors.lastname: Zander
authors.affiliation: Department of Pathology and Laboratory Medicine, Penn State Hershey Medical center, 500 University Drive, Hershey, PA, 17033-0850, USA. nrassaei@hmc.psu.edu.
authors.forename: Negar
authors.initials: N
authors.lastname: Rassaei
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014746:Vimentin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D016212:Transforming Growth Factor beta; D014746:Vimentin; D051176:beta Catenin; D066246:ErbB Receptors
keywords: Diabetes; Epithelial-to-mesenchymal transition; Non-small cell lung cancer