Development and experience of using the transcriptional gene signature in the diagnosis of molecular breast cancer subtypes


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To design and carry out clinical testing a Russian transcriptional gene signature for the diagnosis of molecular breast cancer subtypes. Subjects and methods. The investigation enrolled 168 women aged 29 to 82 years with breast cancer (BC) who had been treated at the Department of Breast Pathology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology. The investigators performed a pathomorphological study of surgical materials and immunohistochemical (IHC) tests for Ki-67, ER, PR, HER2/neu and determined the expression profile of 45 genes of proliferation, apoptosis, invasion, hormone receptors, and growth factor receptors, DNA replication and repair, immunity, transcription factors, and cell differentiation markers by a real-time quantitative polymerase chain reaction assay. Results. The investigators established the main patterns of mRNA expression of the test genes for various BC subtypes and their correlations, devised and tested methods for the molecular genetic classification of breast tumors as compared with the traditional IHC study. Conclusion. The developed transcriptional gene signature reflects the heterogeneity of breast tumors and can be used for their molecular genetic classification.

Full Text

Restricted Access

About the authors

Olga V. Burmenskaya

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: o_bourmenskaya@oparina4.ru
SD, Head of the Laboratory of Oncological Genetics

Dmitry Yu. Trofimov

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: d_trofimov@oparina4.ru
professor, SD, Director of the Institute of Reproductive Genetics

Vlada V. Kometova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_kometova@oparina4.ru
MD, Senior Researcher, Pathology Department

Ilia V. Sergeev

OOO "DNA-Technology Research Production Firm"

Email: i.sergeev@dna-technology.ru
PhD, Head of Oligonucleotide synthesis department

Artem V. Maerle

OOO "DNA-Technology Research Production Firm"

Email: a.maerle@dna-technology.ru
Head of QC unit of Oligonucleotide synthesis department

Valery V. Rodionov

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_rodionov@oparina4.ru
MD, professor, Head of the Department of Breast Cancer Department

Genady T. Sukhikh

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
MD, Academician RAS, professor, Director

References

  1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6): 394424. doi: 10.3322/caac.21492
  2. Perou C.M., Sorlie T., Eisen M.B., et al. Molecular portraits of human breast tumours. Nature. 2000; 406: 747-52. https://doi.org/10.1038/35021093
  3. Paik S., Shak S., Tang G., Kim Ch., et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N. Engl J. Med. 2004; 351(27): 2817-26. doi: 10.1056/NEJMoa041588
  4. Tian S., et al. Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer. Biomark Insights. 2010; 5: 129-38. doi: 10.4137/BMI.S6184
  5. Tian S., Roepman P., Van’t Veer L.J., Bernards R., de Snoo F., Glas A.M., et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast. 2015; 24 Suppl 2: S26-35. doi: 10.4137/BMI.S6184.
  6. Goldhirsch A., Wood W.C., Coates A.S., et al. Strategies for subtypes - dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011; 22: 1736-1747. doi: 10.1093/annonc/mdr304.
  7. Кулигина Е.Ш. Эпидемиологические и молекулярные аспекты рака молочной железы. Практическая онкология. 2010; 11(4): 203-16.
  8. Nielsen T.O., Parker J.S., Leung S., Voduc D., Ebbert M., Vickery T., Davies S.R., Snider J., Stijleman I.J., Reed J., Cheang M.C., Mardis E.R., Perou C.M., Bernard P.S., Ellis M.J. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res. 2010; 16(21): 5222- 32. doi: 10.1158/1078-0432.CCR-10-1282
  9. Guiu S., Michiels S., Andre F., Cortes J., Denkert C., Di Leo A., et al. Molecular subclasses of breast canсer: how do we define them? The IMPAKT 2012 Working Group Statement. Ann Oncol. 2012; 23: 2997-3006. doi: 10.1093/annonc/mds586
  10. Curigliano G., Burstein H.J., Winer E.P., et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017; 28(8):1700-12. doi: 10.1093/annonc/mdx308.
  11. Polley M.Y., Leung S.C., Gao D., et al. An international study to increase concordance in Ki67 scoring. Mod Pathol. 2015; 28: 778-86. doi: 10.1038/ modpathol.2015.38
  12. Polley M.Y., Leung S.C., McShane L.M., et al. An international Ki67 reproducibility study. J. Natl Cancer Inst. 2013; 105: 1897-1906. doi: 10.1093/ jnci/djt306

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Bionika Media

This website uses cookies

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

About Cookies