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Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma

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Tumor Biology

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.

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Acknowledgments

The study has been supported by the Foundation of the Finnish Anti-Tuberculosis Association, the Jalmari and Rauha Ahokas Foundation, the National Graduate School of Clinical Investigation, the Northern Finland Cancer Foundation, the Otto A. Malm Foundation, the Väinö and Laina Kivi Foundation, and the state subsidy for the University Hospital of Oulu. We thank Ms. Riitta Vuento and the Biocenter Oulu EM laboratory staff for technical assistance and Dr. Ewen MacDonald for the language revision.

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Authors and Affiliations

  1. Department of Pathology, Oulu University Hospital, POB 50, 90029, Oulu, Finland

    Elisa Lappi-Blanco, Johanna M. Mäkinen & Raija Sormunen

  2. Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland

    Elisa Lappi-Blanco, Johanna M. Mäkinen & Raija Sormunen

  3. 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, Johanna M. Mäkinen, Siri Lehtonen, Henna Karvonen, Kirsi Laitakari, Shirley Johnson, Riitta Mäkitaro & Riitta Kaarteenaho

  4. 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

    Henna Karvonen

  5. Biocenter Oulu, University of Oulu, Aapistie 5A, 90220, Oulu, Finland

    Raija Sormunen

  6. Department of Medicine, Oulu University Hospital, POB 20, 90029, Oulu, Finland

    Shirley Johnson & Riitta Mäkitaro

  7. Medical Informatics and Statistics Research Group, University of Oulu, POB 5000, 90014, Oulu, Finland

    Risto Bloigu

  8. Unit of Medicine and Clinical Research, Pulmonary Division, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Riitta Kaarteenaho

  9. Center of Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, POB 100, 70029, Kuopio, Finland

    Riitta Kaarteenaho

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  1. Elisa Lappi-Blanco
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  2. Johanna M. Mäkinen
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  6. Kirsi Laitakari
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  7. Shirley Johnson
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Corresponding author

Correspondence to Elisa Lappi-Blanco.

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Ethical statement

Ethical approval for the study was obtained from the Ethical Committee of the Northern Ostrobothnia Hospital District in Oulu (statement 2/2008) and from the National Supervisory Authority for Welfare and Health (formerly the National Authority of Medicolegal Affairs, reg. no. 863/04/047/08).

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Elisa Lappi-Blanco and Johanna M. Mäkinen has equal contribution.

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Lappi-Blanco, E., Mäkinen, J.M., Lehtonen, S. et al. Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. Tumor Biol. 37, 13811–13820 (2016). https://doi.org/10.1007/s13277-016-5269-6

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  • DOI: https://doi.org/10.1007/s13277-016-5269-6

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