Skip to main content

Advertisement

SpringerLink
Log in

Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The goal of this study was to evaluate the expression of MUC1 in stage IB non-small cell lung cancer (NSCLC) and its prognostic significance. The expression of MUC1 in 178 NSCLC specimens was evaluated via immunohistochemistry. A reproducible semiquantitative method which took both staining percentage and intensity into account was applied for immunohistochemical scoring, and receiver operating characteristic curve analysis was utilized to select the cut-off score for high or low MUC1 expression. Then, the correlations between MUC1 expression and clinicopathological features and its prognostic relevance were determined. In this study, high MUC1 expression was detected more frequently in adenocarcinomas (86.3%) and other NSCLCs (74.1%) than in squamous cell carcinomas (39.1%, P < 0.001). The Kaplan–Meier survival curves showed that up-regulated expression of MUC1 indicated poorer overall survival (OS) and disease-free survival (DFS) (P = 0.011 and P = 0.008, respectively), especially for those with non-squamous cell carcinomas (P = 0.033 and P = 0.011, respectively). Multivariate analysis also confirmed that MUC1 expression was an independent prognostic factor for both OS and DFS in stage IB NSCLC (P = 0.008 and P = 0.004, respectively). MUC1 might be correlated with the histogenesis of lung adenocarcinoma, and its elevated expression may be an adverse prognostic indicator for the patients with stages IB NSCLC, particularly for those with non-squamous cell carcinomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Strauss GM, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage ib non-small-cell lung cancer: Calgb 9633 with the cancer and leukemia group b, radiation therapy oncology group, and north central cancer treatment group study groups. J Clin Oncol. 2008;26:5043–51.

    Article  PubMed  CAS  Google Scholar 

  3. Zeng W, et al. Hepatocellular carcinomas in cirrhotic and noncirrhotic human livers share angiogenic characteristics. Ann Surg Oncol. 2010;17:1564–71.

    Article  PubMed  Google Scholar 

  4. Patton S, Gendler SJ, Spicer AP. The epithelial mucin, muc1, of milk, mammary gland and other tissues. Biochim Biophys Acta. 1995;1241:407–23.

    PubMed  CAS  Google Scholar 

  5. Guddo F, et al. Muc1 (episialin) expression in non-small cell lung cancer is independent of egfr and c-erbb-2 expression and correlates with poor survival in node positive patients. J Clin Pathol. 1998;51:667–71.

    Article  PubMed  CAS  Google Scholar 

  6. Guddo F, et al. Depolarized expression of episialin (ema, muc1) in lung adenocarcinoma is associated with tumor progression. Anticancer Res. 1998;18:1915–20.

    PubMed  CAS  Google Scholar 

  7. Wesseling J, van der Valk SW, Hilkens J. A mechanism for inhibition of e-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/muc1. Mol Biol Cell. 1996;7:565–77.

    PubMed  CAS  Google Scholar 

  8. Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J. Episialin (muc1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol. 1995;129:255–65.

    Article  PubMed  CAS  Google Scholar 

  9. Pandey P, Kharbanda S, Kufe D. Association of the df3/muc1 breast cancer antigen with grb2 and the sos/ras exchange protein. Cancer Res. 1995;55:4000–3.

    PubMed  CAS  Google Scholar 

  10. Li Y, et al. The epidermal growth factor receptor regulates interaction of the human df3/muc1 carcinoma antigen with c-src and beta-catenin. J Biol Chem. 2001;276:35239–42.

    Article  PubMed  CAS  Google Scholar 

  11. Ren J, Li Y, Kufe D. Protein kinase c delta regulates function of the df3/muc1 carcinoma antigen in beta-catenin signaling. J Biol Chem. 2002;277:17616–22.

    Article  PubMed  CAS  Google Scholar 

  12. Khodarev N, et al. Cooperativity of the muc1 oncoprotein and stat1 pathway in poor prognosis human breast cancer. Oncogene. 2010;29:920–9.

    Article  PubMed  CAS  Google Scholar 

  13. Fessler SP, Wotkowicz MT, Mahanta SK, Bamdad C. Muc1* is a determinant of trastuzumab (herceptin) resistance in breast cancer cells. Breast Cancer Res Treat. 2009;118:113–24.

    Article  PubMed  CAS  Google Scholar 

  14. Piessen G, et al. Clinical impact of muc1 and muc4 expression in barrett-associated oesophageal adenocarcinoma. J Clin Pathol. 2009;62:1144–6.

    Article  PubMed  CAS  Google Scholar 

  15. Levi E, Klimstra DS, Andea A, Basturk O, Adsay NV. Muc1 and muc2 in pancreatic neoplasia. J Clin Pathol. 2004;57:456–62.

    Article  PubMed  CAS  Google Scholar 

  16. Baldus SE, et al. Muc1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res. 2004;10:2790–6.

    Article  PubMed  CAS  Google Scholar 

  17. Medina M, et al. Human colon adenocarcinomas express a muc1-associated novel carbohydrate epitope on core mucin glycans defined by a monoclonal antibody (a10) raised against murine ehrlich tumor cells. Cancer Res. 1999;59:1061–70.

    PubMed  CAS  Google Scholar 

  18. Wang RQ, Fang DC. Alterations of muc1 and muc3 expression in gastric carcinoma: Relevance to patient clinicopathological features. J Clin Pathol. 2003;56:378–84.

    Article  PubMed  Google Scholar 

  19. Obermair A, et al. Expression of muc1 splice variants in benign and malignant ovarian tumours. Int J Cancer. 2002;100:166–71.

    Article  PubMed  CAS  Google Scholar 

  20. Rassidakis GZ, et al. Prognostic significance of muc-1 expression in systemic anaplastic large cell lymphoma. Clin Cancer Res. 2003;9:2213–20.

    PubMed  CAS  Google Scholar 

  21. Awaya H, Takeshima Y, Yamasaki M, Inai K. Expression of muc1, muc2, muc5ac, and muc6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung. Am J Clin Pathol. 2004;121:644–53.

    Article  PubMed  CAS  Google Scholar 

  22. Nagai S, et al. A novel classification of muc1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer. J Thorac Oncol. 2006;1:46–51.

    Article  PubMed  Google Scholar 

  23. Jarrard JA, et al. Muc1 is a novel marker for the type ii pneumocyte lineage during lung carcinogenesis. Cancer Res. 1998;58:5582–9.

    PubMed  CAS  Google Scholar 

  24. Zhu ZH, et al. Three immunomarker support vector machines-based prognostic classifiers for stage ib non-small-cell lung cancer. J Clin Oncol. 2009;27:1091–9.

    Article  PubMed  Google Scholar 

  25. Hanley JA. Receiver operating characteristic (roc) methodology: the state of the art. Crit Rev Diagn Imag. 1989;29:307–35.

    CAS  Google Scholar 

  26. Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60:1112–6.

    Article  PubMed  Google Scholar 

  27. Woenckhaus M, et al. Prognostic value of fhit, ctnnb1, and muc1 expression in non-small cell lung cancer. Hum Pathol. 2008;39:126–36.

    Article  PubMed  CAS  Google Scholar 

  28. Ohgami A, et al. Muc1 mucin mrna expression in stage i lung adenocarcinoma and its association with early recurrence. Ann Thorac Surg. 1999;67:810–4.

    Article  PubMed  CAS  Google Scholar 

  29. Giatromanolaki A, et al. Coexpression of muc1 glycoprotein with multiple angiogenic factors in non-small cell lung cancer suggests coactivation of angiogenic and migration pathways. Clin Cancer Res. 2000;6:1917–21.

    PubMed  CAS  Google Scholar 

  30. Tsutsumida H, et al. Combined status of muc1 mucin and surfactant apoprotein a expression can predict the outcome of patients with small-size lung adenocarcinoma. Histopathology. 2004;44:147–55.

    Article  PubMed  CAS  Google Scholar 

  31. Salaun B, et al. Cd208/dendritic cell-lysosomal associated membrane protein is a marker of normal and transformed type ii pneumocytes. Am J Pathol. 2004;164:861–71.

    Article  PubMed  CAS  Google Scholar 

  32. Ueno T, Linder S, Elmberger G. Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer. 2003;88:1229–33.

    Article  PubMed  CAS  Google Scholar 

  33. Gendler SJ. Muc1, the renaissance molecule. J Mammary Gland Biol Neoplasia. 2001;6:339–53.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Cancer Center, Sun Yat-Sen University, 651, Dongfeng Road East, 510060, Guangzhou, People’s Republic of China

    Dongrong Situ, Zhihua Zhu, Yi Hu, Hao Long & Tiehua Rong

  2. Department of Anesthesia, Cancer Center, Sun Yat-Sen University, 651, Dongfeng Road East, 510060, Guangzhou, People’s Republic of China

    Jian Wang

  3. Reproductive Research Center, The Second Affiliated Hospital, Sun Yat-Sen University, 107, Yanjiang Road West, 510120, Guangzhou, People’s Republic of China

    Yun Ma

Authors
  1. Dongrong Situ
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhihua Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hao Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tiehua Rong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhihua Zhu.

Additional information

Dongrong Situ, Jian Wang and Yun Ma contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Situ, D., Wang, J., Ma, Y. et al. Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol 28 (Suppl 1), 596–604 (2011). https://doi.org/10.1007/s12032-010-9752-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9752-4

Keywords

Search

Navigation