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Prognostic analysis of primary mucin-producing adenocarcinoma of the lung: a comprehensive retrospective study

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Tumor Biology

Abstract

Although primary mucin-producing adenocarcinoma of the lung is uncommon, each subtype has distinct clinical, pathological, molecular, and prognostic characteristics. This study aimed to determine correlations between clinical and pathological features and genetic phenotypes with the prognosis. We immunohistochemically examined the protein levels of thyroid transcription factor 1 (TTF-1), Napsin A, and anaplastic lymphoma kinase (ALK) and genetically examined epidermal growth factor receptor (EGFR) and KRAS mutations in these mucin-producing tumors. A total of 75 cases of mucin-producing adenocarcinoma of the lung were examined. ALK protein positivity was 33.3 % (25/75), and primarily occurred in solid predominant with mucin production subtype (SA). KRAS mutations occurred in 22.7 % (17/75) of patients, predominantly in invasive mucinous adenocarcinoma (IMA). Positive TTF-1 and Napsin A expression was more common in SA, while they were both negative in IMA. The 1-, 3-, and 5-year progression-free survival rates of mucin-producing lung adenocarcinoma were 85, 64, and 38 %, respectively; the overall survival rates were 90, 67, and 50 %, respectively. Larger tumors, advanced stage, and lymph node metastasis were associated with poor prognosis. Mucinous minimally invasive adenocarcinoma (m-MIA) had the best prognosis, followed by IMA, SA, and acinar or papillary predominant adenocarcinoma with mucin production (A/P). KRAS mutations were an independent positive prognostic factor for postoperative progress.

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References

  1. Rossi G, Sartori G, Murer B, et al. Mucin-rich tumors of the lung. Am J Clin Pathol. 2007;127(3):473–4. author reply 474.

  2. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zhang P, Han YP, Huang L, et al. Value of napsin A and thyroid transcription factor-1 in the identification of primary lung adenocarcinoma. Oncol Lett. 2010;1(5):899–903.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wu J, Chu PG, Jiang Z, et al. Napsin A expression in primary mucin-producing adenocarcinomas of the lung: an immunohistochemical study. Am J Clin Pathol. 2013;139(2):160–6.

    Article  PubMed  Google Scholar 

  5. Iqbal J. Role of Napsin A and TTF-1 as a diagnostic marker for lung adenocarcinoma. Arch Pathol Lab Med. 2013;137(2):155.

    Article  PubMed  Google Scholar 

  6. Tsuta K, Ishii G, Nitadori J, et al. Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin. J Pathol. 2006;209(1):78–87.

    Article  CAS  PubMed  Google Scholar 

  7. Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res. 2007;13(10):2890–6.

    Article  CAS  PubMed  Google Scholar 

  8. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. Plos Med. 2005;2:e17.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yoshizawa A, Motoi N, Riely GJ, et al. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol. 2011;24(5):653–64.

    Article  CAS  PubMed  Google Scholar 

  10. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J ClinOncol. 2009;27:4247–53.

    Article  CAS  Google Scholar 

  11. Rossi G, Murer B, Cavazza A, et al. Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol. 2004;28(4):442–52.

    Article  PubMed  Google Scholar 

  12. Conde E, Suárez-Gauthier A, Benito A, et al. Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry. PLoS One. 2014;9:e107200.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.

    Article  CAS  PubMed  Google Scholar 

  15. Kim MH, Shim HS, Kang DR, et al. Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma. Lung Cancer. 2014;83(3):389–95.

    Article  PubMed  Google Scholar 

  16. Lau SK, Desrochers MJ, Luthringer DJ. Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases. Mod Pathol. 2002;15(5):538–42.

    Article  PubMed  Google Scholar 

  17. Ordóñez NG. Napsin A, expression in lung and kidney neoplasia: a review and update. Adv Anat Pathol. 2012;19(1):66–73.

    Article  PubMed  Google Scholar 

  18. Ichinokawa H, Ishii G, Nagai K, et al. Distinct clinicopathologic characteristics of lung mucinous adenocarcinoma with KRAS mutation. Hum Pathol. 2013;44(12):2636–42.

    Article  CAS  PubMed  Google Scholar 

  19. Kadota K, Yeh Y-C, D'Angelo SP, et al. Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation. Am J Surg Pathol. 2014;38:1118–27.

  20. Macerelli M, Caramella C, Faivre L, et al. Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)? Lung Cancer. 2014;83(3):383–8.

    Article  CAS  PubMed  Google Scholar 

  21. Cadranel J, Mauguen A, Faller M, et al. Impact of systematic EGFR and KRAS mutation evaluation on progression-free survival and overall survival in patients with advanced non-small-cell lung cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part 2). J Thorac Oncol. 2012;7(10):1490–502.

    Article  CAS  PubMed  Google Scholar 

  22. Meng D, Yuan M, Li X, et al. Prognostic value of K-RAS mutations in patients with non-small cell lung cancer: a systematic review with meta-analysis. Lung Cancer. 2013;81(1):1–10.

    Article  PubMed  Google Scholar 

  23. Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer. 1995;75(12):2844–52.

    Article  CAS  PubMed  Google Scholar 

  24. Kadota K, Villena-Vargas J, Yoshizawa A, et al. Prognostic significance of adenocarcinoma in situ, minimally invasive adenocarcinoma, and nonmucinous lepidic predominant invasive adenocarcinoma of the lung in patients with stage I disease. Am J Surg Pathol. 2014;38(4):448–60.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cha MJ, Lee HY, Lee KS, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg. 2014;147(3):921–8. e2.

    Article  PubMed  Google Scholar 

  26. Hung JJ, Jeng WJ, Chou TY, et al. Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma. Ann Surg. 2013;258(6):1079–86.

    Article  PubMed  Google Scholar 

  27. Warth A, Muley T, Meister M, et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol. 2012;30(13):1438–46.

    Article  PubMed  Google Scholar 

  28. Lakshmanan I, Ponnusamy MP, Macha MA, et al. Mucins in lung Cancer: Diagnostic, Prognostic and Therapeutic Implications. J Thorac Oncol. 2014;10(1):19–27.

    Article  Google Scholar 

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Acknowledgements

This study was supported by a grant from the Magor Programs of Beijing Municipal Science and Technology Commission (D141100000214003).

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Authors and Affiliations

  1. Department of Pathology, The General Hospital of People’s Liberation Army, 28# Fuxing Road, Haidian District, Beijing, 100853, China

    Yang Qu & Lixin Wei

  2. Department of pathology, Beijing Chest Hospital, Capital Medical University, 97# Machang, Tongzhou District, Beijing, 101149, China

    Yang Qu, Dan Zhao, Jing Mu, Nanying Che, Chen Zhang, Zichen Liu, Dan Su, Lijuan Zhou & Haiqing Zhang

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  1. Yang Qu
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  2. Dan Zhao
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Correspondence to Haiqing Zhang or Lixin Wei.

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Qu, Y., Zhao, D., Mu, J. et al. Prognostic analysis of primary mucin-producing adenocarcinoma of the lung: a comprehensive retrospective study. Tumor Biol. 37, 887–896 (2016). https://doi.org/10.1007/s13277-015-3869-1

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  • DOI: https://doi.org/10.1007/s13277-015-3869-1

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