title: Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma.
abstract: Mucin-1 (MUC1) affects cancer progression in lung adenocarcinoma, and its aberrant expression pattern has been correlated with poor tumor differentiation and impaired prognosis. In this study, the immunohistochemical expression of MUC1 and Mucin-4 (MUC4) was analyzed in a series of 106 surgically operated stage I-IV pulmonary adenocarcinomas. MUC1 immunohistochemistry was evaluated according to the Nagai classification, and the immunohistochemical profile of the tumors was correlated with detailed clinical and histological data. The effect of cigarette smoke on MUC1 expression in lung cancer cell lines was examined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoelectron microscopy (IEM). In contrast to the normal apical localization of MUC1, a basolateral and cytoplasmic (depolarized) MUC1 expression pattern was frequently encountered in the high-grade subtypes, i.e., solid predominant adenocarcinoma and the cribriform variant of acinar predominant adenocarcinoma (p < 0.001), and was rarely observed in tumors containing a non-predominant lepidic component (p < 0.001). Furthermore, the altered staining pattern of MUC1 correlated with stage (p = 0.002), reduced overall survival (p = 0.031), and was associated with smoking (p < 0.001). When H1650 adenocarcinoma cells were exposed to cigarette smoke and analyzed by RT-qPCR and IEM, the levels of the MUC1 transcript and protein were elevated (p = 0.042). In conclusion, MUC1 participates in the pathogenesis of lung adenocarcinoma and associates with smoking both in vitro and in vivo. In lung adenocarcinoma, depolarized MUC1 protein expression correlated with histological growth patterns, stage, and patient outcome.
authors.affiliation: Department of Pathology, Oulu University Hospital, POB 50, 90029, Oulu, Finland. elisa.lappi-blanco@ppshp.fi.|Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland. elisa.lappi-blanco@ppshp.fi.|Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland. elisa.lappi-blanco@ppshp.fi.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.affiliation: Department of Pathology, Oulu University Hospital, POB 50, 90029, Oulu, Finland.|Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland.|Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Mäkinen
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.
authors.forename: Siri
authors.initials: S
authors.lastname: Lehtonen
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.|Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 234, 150 College St, Toronto, ON, M5S 3E2, Canada.
authors.forename: Henna
authors.initials: H
authors.lastname: Karvonen
authors.affiliation: Department of Pathology, Oulu University Hospital, POB 50, 90029, Oulu, Finland.|Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland.|Biocenter Oulu, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Laitakari
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.|Department of Medicine, Oulu University Hospital, POB 20, 90029, Oulu, Finland.
authors.forename: Shirley
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.|Department of Medicine, Oulu University Hospital, POB 20, 90029, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Mäkitaro
authors.affiliation: Medical Informatics and Statistics Research Group, University of Oulu, POB 5000, 90014, Oulu, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.affiliation: Respiratory Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029, Oulu, Finland.|Unit of Medicine and Clinical Research, Pulmonary Division, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.|Center of Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, POB 100, 70029, Kuopio, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D008297:Male; D016253:Microscopy, Immunoelectron; D018396:Mucin-1 / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D012333:RNA, Messenger
keywords: IEM; Immunohistochemistry; Lung adenocarcinoma; MUC1; RT-qPCR; Smoking