INTERRELATION OF THE EXPRESSION OF PROTEINS ALK, HER2 AND AMPLIFICATION OF THE GENE OF HER2 WITH THE PROLIFERATIVE ACTIVITY AND SURVIVAL IN PATIENTS WITH STAGE I-II LUNG ADENOCARCINOMA


Cite item

Full Text

Abstract

To investigate protein content of ALK, Her2 and gene of Her2, CEP17 in interrelation with proliferative activity and survival in I-II stages lung adenocarcinoma cases. There were investigated 82 surgery samples taken from I-II stage lung adenocarcinoma patients. With the use of immunohistochemical method ALK protein (clone D5F3, Ventana), Her2 protein (clone 4B5, Ventana), topoizomerase IIα (clone JS5B4, Ventana), Ki-67 (clone MIB-1, Dako) were determined, Her2 gene was investigated with the use of the SISH method (Ventana) also. The positive expression of ALK is detected in 4(5%) cases, Her2 - in 16(20%) cases and amplification of Her2 gene - in 7(9%) cases. In lung adenocarcinoma with positive expression of ALK protein and amplification of Her2 gene low proliferative activity was noted (on labeling index Ki-67 and topoizomerase IIα). The survival of lung adenocarcinoma patients was less in cases of a positive expression of ALK protein in comparison with patients with the negative expression (difference is not reliable). Statistically significant low survival rates of patients is found in cases with amplification of Her2 gene. According to data mono- and multifactor regression analysis the amplification of Her2 gene has been interrelated with the poor forecast. Mutation of ALK gene and amplification of Her2 gene are interrelated with the proliferative activity and survival rate of lung adenocarcinoma patients.

About the authors

Artak U. Panas’yan

Altai branch of the N.N. Blokhin Russian Cancer Research Center; Altai Krai Oncology Centre

Email: urartu26@yandex.ru
MD, Researcher of the Department for the Development of Modern Methods of Treatment in Thoracic Oncology of the Altai Branch of the N.N. Blokhin Russian Cancer Research Center; Barnaul, 656049, Russian Federation Barnaul, 656049, Russian Federation; Barnaul, 656043, Russian Federation

D. S Kobyakov

Kogalym municipal hospital

Kogalym, 628481, Russian Federation

A. M Avdalyan

Altai branch of the N.N. Blokhin Russian Cancer Research Center

Barnaul, 656049, Russian Federation

A. A Ivanov

Altai branch of the N.N. Blokhin Russian Cancer Research Center

Barnaul, 656049, Russian Federation

E. L Lushnikova

Institute of Molecular Pathology and Pathomorphology

Novosibirsk, 630117, Russian Federation

M. A Bakarev

Institute of Molecular Pathology and Pathomorphology

Novosibirsk, 630117, Russian Federation

A. F Lazarev

Altai branch of the N.N. Blokhin Russian Cancer Research Center

Barnaul, 656049, Russian Federation

References

  1. Warth A., Penzel R., Lindenmaier H., Brandt R., Stenzinger A., Herpel E. et al. EGFR, KRAS, BRAF and ALK gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype. Eur. Respir. J. 2014; 43: 872-3.
  2. Zhao F., Xu M., Lei H., Zhou Z., Wang L., Li P. et al. Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusiongene: a meta-analysis. PLoS One. 2015; 10(2): e0117333.
  3. Nakamura H., Saji H., Ogata A., Hosaka M., Hagiwara M., Kawasaki N. et al. Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non-small cell lung cancer. Int. J. Cancer. 2003; 103: 61-6.
  4. Al-Saad S., Al-Shibli K., Donnem T., Andersen S., Bremnes R.M., Busund L.T. Clinical significance of epidermal growth factor receptors in non-small cell lung cancer and a prognostic role for HER2 gene copy number in female patients. J. Thorac. Oncol. 2010; 5: 1536-43.
  5. Beresford M.J., Wilson G.D., Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res. 2006; 8: 216.
  6. Jakobsen J.N., Sorensen J.B. Clinical impact of Ki-67 labeling index in non-small cell lung cancer. Lung Cancer. 2013; 79: 1-7.
  7. Del Gobbo A., Pellegrinelli A., Gaudioso G., Castellani M., Zito Marino F., Franco R. et al. Analysis of NSCLC tumour heterogeneity, proliferative and 18F-FDG PET indices reveals Ki67 prognostic role in adenocarcinomas. Histopathology. 2016; 68: 746-51.
  8. Pelosi G., Del Curto B., Dell’Orto P., Pasini F., Veronesi G., Spaggiari L. et al. Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung. Int. J. Cancer. 2005; 113: 101-8.
  9. Tan D., Deeb G., Wang J., Slocum H.K., Winston J., Wiseman S. et al. HER-2/neu protein expression and gene alteration in stage I-IIIA nonsmall-cell lung cancer: a study of 140 cases using a combination of high throughput tissue microarray, immunohistochemistry, and fluorescent in situ hybridization. Diagn. Mol. Pathol. 2003; 12: 201-11.
  10. Yang P., Kulig K., Boland J.M., Erickson-Johnson M.R., Oliveira A.M., Wampfler J. et al. Worse disease-free survival in never-smokers with ALK lung adenocarcinoma. J. Thorac. Oncol. 2012; 7: 90-7.
  11. Lee J.K., Park H.S., Kim D.W., Kulig K., Kim T.M., Lee S.H. et al. Comparative analyses of overall survival in patients with anaplastic lymphoma kinase-positive and matched wild-type advanced nonsmall cell lung cancer. Cancer. 2012; 118: 3579-86.
  12. Wu S.G., Kuo Y.W., Chang Y.L., Shih J.Y., Chen Y.H., Tsai M.F. et al. EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR. J. Thorac. Oncol. 2012; 7: 98-104.
  13. Sobin L., Gospodarowicz M., Wittekind C. (Eds.). TNM Classification of Malignant Tumours. 7th Ed. Oxford: Wiley-Blackwell; 2009: 138-46.
  14. Travis W.D., Brambilla E., Noguchi M., Nicholson A.G., Geisinger K.R., Yatabe Y. 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: 244-85.
  15. Hofmann M., Stoss O., Shi D., Bьttner R., van de Vijver M., Kim W. et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008; 52: 797-805.
  16. Wang S., Hossein Saboorian M., Frenkel E.P., Haley B.B., Siddiqui M.T., Gokaslan S. et al. Aneusomy 17 in breast cancer: its role in HER-2/neu protein expression and implication for clinical assessment of HER-2/neu status. Mod. Pathol. 2002; 15: 137-45.
  17. Siraj A.K., Beg S., Jehan Z., Prabhakaran S., Ahmed M., Hussain A.R. et al. ALK alteration is a frequent event in aggressive breast cancers. Breast Cancer Res. 2015; 17: 127.
  18. Shokouh T.Z., Ezatollah A., Barand P. Interrelationships between Ki67, HER2/neu, p53, ER, and PR status and their associations with tumor grade and lymph node involvement in breast carcinoma subtypes: retrospective-observational analytical study. Medicine (Baltimore). 2015; 94: e1359.
  19. Nogi H., Uchida K., Kamio M., Kato K., Toriumi Y., Akiba T. et al. Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIб. Mol. Clin. Oncol. 2016; 4: 383-9.
  20. Payandeh M., Shahriari-Ahmadi A., Sadeghi M., Sadeghi E. Correlations between HER2 expression and other prognostic factors in breast cancer: Inverse relations with the Ki-67 index and P53 status. Asian. Pac. J. Cancer Prev. 2016; 17: 1015-8.

Copyright (c) 2017 Eco-Vector


 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies