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Overexpression of c-erbB-2 and loss of p16 have molecular diagnostic relevance but no prognostic value in lung cancer

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Abstract

This study was designed to evaluate the expression of C-erbB-2 and p16 in lung cancers using tissue microarray technology and to determine their clinical and pathological significance. Immunohistochemical C-erbB-2 and p16 expressions and their associations with clinical and pathological features were analyzed in two tissue microarrays. The membranous and cytoplasmic expression rates of C-erbB-2 were 40.5 and 66.5% in non-small cell lung cancers (NSCLCs), and 0 and 9.5% in small cell lung cancers (SCLCs), respectively. The nuclear and cytoplasmic expression rates of p16 were 11.5 and 32.2% in NSCLs, and 45 and 80% in SCLCs, respectively. The cytoplasmic expression of both C-erbB-2 and p16 was more frequent than the membranous expression of C-erbB-2 and the nuclear expression of p16. The rates of overexpression of C-erbB-2 and loss of p16 expression were significantly higher in NSCLCs than in SCLCs (P < 0.05). Neither C-erbB-2 nor p16 expression was significantly associated with age, tumor grade or stage, presence of lymph node metastasis or survival duration. The abnormal expressions of p16 and C-erbB-2 may play a role in the progression of lung cancers. The variations in the expression patterns of C-erbB-2 and p16 between NSCLCs and SCLCs may aid the molecular classification of lung cancer. The abnormal expression of p16 may be involved in the development of NSCLCs, and the overexpression of C-erbB-2 in NSCLCs indicates that it can be a candidate target for gene therapy.

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References

  1. Li L, Lu F, Zhang S. Analyses of variation trend and short-term detection of Chinese malignant tumor mortality during twenty years. Zhonghua Zhong Liu Za Zhi. 1997;19:3–9.

    PubMed  CAS  Google Scholar 

  2. Ferretti G, Felici A, Papaldo P, Fabi A, Cognetti F. HER2/neu role in breast cancer: from a prognostic foe to a predictive friend. Curr Opin Obstet Gynecol. 2007;19:56–62.

    Article  PubMed  Google Scholar 

  3. Liang J, Mittal KR, Wei JJ, Yee H, Chiriboga L, Shukla P. Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the differential diagnosis of benign, premalignant, and malignant glandular lesions of the uterine cervix and their relationship with Silverberg scoring system for endocervical glandular lesions. Int J Gynecol Pathol. 2007;26:71–5.

    Article  PubMed  Google Scholar 

  4. Travis WD, Colby TV, Corrin B, et al. World health organization international histological classification of tumours: histological typing of lung and pleural tumours. 3rd ed. Berlin, Germany: Springer; 1999.

    Google Scholar 

  5. SPSS Inc. SPSS Base10.0 Applications Guide. Chicago, IL: SPSS Inc.; 1999.

    Google Scholar 

  6. Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1711–7.

    Google Scholar 

  7. Hirsch FR, Langer CJ. The role of HER2/neu expression and trastuzumab in non-small cell lung cancer. Semin Oncol. 2004;31:75–82.

    Article  PubMed  CAS  Google Scholar 

  8. Ugocsai K, Mándoky L, Tiszlavicz L, Molnár J. Investigation of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2005;25:3061–6.

    PubMed  CAS  Google Scholar 

  9. Calikusu Z, Yildirim Y, Akcali Z, Sakalli H, Bal N, Ozyilkan O. Prognostic significance of the C-erbB-2 expression in turkish non-small cell lung cancer patients. Asian Pac J Cancer Prev. 2009;10:479–82.

    PubMed  Google Scholar 

  10. Seidenfeld J, Samsom DJ, Rothenberg BM, Bonnell CJ, Ziegler KM. Aronson N HER2 testing to manage patients with breast cancer or other solid tumors. Evid Rep Technol Assess (Full Rep). 2008;172:1–362.

    Google Scholar 

  11. Papila C, Uzun H, Balci H, Zerdali H, Sezgin C, Can G, et al. Clinical significance and prognostic value of serum sHER-2/neu levels in patients with solid tumors. Med Oncol. 2009;26:151–6.

    Article  PubMed  CAS  Google Scholar 

  12. Feng XL, Zhang XB, Wan YX, Ma JH, Sun YT. Expressions of C-erbB-2 protein in tissues and cell lines of renal cell carcinoma. Chin J Pathol. 2002;31:158–9.

    Google Scholar 

  13. Reinmuth N, Brandt B, Kunze WP, Junker K, Thomas M, Achatzy R, et al. Ploidy, expression of erbB1, erbB-2, P53 and amplification of erbB1, erbB2, and erbB3 in non-small cell lung cancer. Eur Respir J. 2000;16:991–6.

    Article  PubMed  CAS  Google Scholar 

  14. Cheng CM, Tsuneyama K, Matsui K, Takahashi H, Ishizawa S, Takano Y. Cytoplasmic expression of c-erbB2 in non-small cell lung cancers. Virchows Arch. 2005;446:596–603.

    Article  PubMed  CAS  Google Scholar 

  15. Wikenheiser-Brokamp KA. Retinoblastoma regulatory pathway in lung cancer. Curr Mol Med. 2006;6:783–93.

    PubMed  CAS  Google Scholar 

  16. Esposito V, Baldi A, De Luca A, Tonini G, Vincenzi B, Santini D, et al. Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer. J Clin Pathol. 2005;58:734–9.

    Article  PubMed  CAS  Google Scholar 

  17. Sanz-Ortega J, Roig F, Al-Mousa MM, Saez MC, Muñoz A, Sanz-Esponera J, et al. 17p13 (p53 locus), 5q21 (APC locus) and 9p21 (p16 locus) allelic deletions are frequently found in oral exfoliative cytology cells from smoker patients with non-small-cell lung cancer. Histol Histopathol. 2007;22:541–5.

    PubMed  CAS  Google Scholar 

  18. Ho WL, Chang JW, Tseng RC, Chen JT, Chen CY, Jou YS, et al. Loss of heterozygosity at loci of candidate tumor suppressor genes in microdissected primary non-small cell lung cancer. Cancer Detect Prev. 2002;26:343–9.

    Article  PubMed  CAS  Google Scholar 

  19. Nakata S, Sugio K, Uramoto H, Oyama T, Hanagiri T, Morita M, et al. The methylation status and protein expression of CDH1, p16 (INK4A), and fragile histidine triad in non-small cell lung carcinoma: epigenetic silencing, clinical features, and prognostic significance. Cancer. 2006;106:2190–9.

    Article  PubMed  CAS  Google Scholar 

  20. Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005;11:3974–86.

    Article  PubMed  CAS  Google Scholar 

  21. Abdulkader I, Sánchez L, Cameselle-Teijeiro J, Gude F, Chávez JE, López-López R, et al. Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study. Oncol Rep. 2005;14:1527–31.

    PubMed  CAS  Google Scholar 

  22. Evangelou K, Bramis J, Peros I, Zacharatos P, Dasiou-Plakida D, Kalogeropoulos N, et al. Electron microscopy evidence that cytoplasmic localization of the p16(INK4A) “nuclear” cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas. Biotech Histochem. 2004;79:5–10.

    Article  PubMed  CAS  Google Scholar 

  23. Milde-Langosch K, Bamberger AM, Rieck G, Kelp B, Loning T. Overexpression of the p16 cell cycle inhibitor in breast cancer is associated with a more malignant phenotype. Breast Cancer Res Treat. 2001;67:61–70.

    Article  PubMed  CAS  Google Scholar 

  24. Zhao P, Hu YC, Talbot IC. Expressing patterns of p16 and CDk4 correlated to prognosis in colorectal carcinoma. World J Gastroenterol. 2003;9:2202–6.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Chinese National Nature Science Foundation (No. 30270582).

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Authors and Affiliations

  1. Department of Pathology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, 100021, Beijing, People’s Republic of China

    Xiao-li Feng, Ling Li, Jian-ming Ying & Yun-tian Sun

  2. Department of Pathogeny, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, 100021, Beijing, People’s Republic of China

    Yan-ning Gao, Jian-jun Zhang, Ting Xiao & Shu-jun Cheng

  3. Department of Abdomen Surgery, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, 100021, Beijing, People’s Republic of China

    Ji-dong Gao

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  1. Xiao-li Feng
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Correspondence to Xiao-li Feng.

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Feng, Xl., Li, L., Gao, Yn. et al. Overexpression of c-erbB-2 and loss of p16 have molecular diagnostic relevance but no prognostic value in lung cancer. Med Oncol 28, 336–341 (2011). https://doi.org/10.1007/s12032-010-9452-0

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  • DOI: https://doi.org/10.1007/s12032-010-9452-0

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