Molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer patients

Dergunova Yu.A., Bozhenko V.K., Podionov V.V., Kometova V.V., Makarova M.V., Ashrafyan L.A.

1) Regional Clinical Oncology Dispensary, Ulyanovsk, Russia; 2) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia; 3) Russian Research Center of Roentgenology and Radiology, Ministry of Health of the Russian Federation, Moscow, Russia
Objective. To identify molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer (BC) on the basis of the gene-expression profiling analysis of primary tumors. Subjects and methods. The investigation enrolled 200 patients with morphologically verified unicentric invasive BC (T1-4N0-3M0,) who had been treated at the Ulyanovsk Regional Clinical Oncology Dispensary in 2012 to 2015. A tumor tissue molecular genetic study was performed using reverse transcription-polymerase chain reaction (RT-PCR) assay; a diagnostic panel consisted of 28 functional genes. Results. In the metastatic regional lymph node involvement group, the primary breast tumor was characterized by enhanced proliferative activity in terms of the expression of the Ki-67 gene (p = 0.028) and by the higher mRNA levels of the NAT (p = 0.039) and CD68 (p <0.001) genes with a reduction in PTEN expression (p <0.001) and with decreased ESR1 gene expression (p = 0.043). A discriminant analysis showed that the accuracy in predicting the presence or absence of metastatic regional lymph node involvement on the basis of a primary tumor molecular genetic study using a 7-gene expression panel was 91.9 and 78.8%, respectively. Conclusion. The primary breast tumor tissue molecular genetic study involving a set of 7 genes (PTEN, CD68, CCNB1, MGB1, MYC, BCL2, and ESR1) can become an additional diagnostic tool for assessing the presence of metastatic lymph node involvement when planning the volume of axillary lymph node dissection in BC patients.

Keywords

breast cancer
molecular genetic prognostic factors
gene expression profiling
mRNA
lymph node dissection
local recurrence
lymphogenous metastasis
discriminant analysis

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Received 18.09.2020

Accepted 04.10.2020

About the Authors

Julia A. Dergunova, pathologist at the pathological department of the State Health Institution Regional Clinical Oncology Center. Tel.: +79603708483.
E-mail: dergunova.yu@mail.ru; https://orcid.org/0000-0002-7499-2650
432017 Russia, Ulyanovsk, st. 12 September, d. 90.
Vladimir K. Bozhenko, MD, professor, consultant to the director of the National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakova Ministry of Health of Russia. Head of the Department of Molecular Biology and Experimental Therapy, Federal State Budgetary Institution Russian Scientific Center for X-ray Radiology, Ministry of Health of Russia. Phone: + 79037996484. E-mail: vbojenko@mail.ru; https://orcid.org/0000-0001-8351-8152
117997 Russia, Moscow, ul. Academician Oparin, d. 4; 117997 Russia, GSP-7, Moscow, ul. Profsoyuznaya, 86.
Valery V. Rodionov, MD, Head of the Department of Breast Pathology, Federal State Budgetary Institution National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakova Ministry of Health of Russia. Tel.: +79266293400. E-mail: dr.valery.rodionov@gmail.com;
https://orcid.org/0000-0003-0096-7126
117997 Russia, Moscow, ul. Academician Oparin, d.4.
Maria V. Makarova, graduate student of the Department of Oncology and X-ray Radiology MI RUDN University on the basis of the Federal State Budgetary Institution Russian Scientific Center for Radiological Radiology of the Ministry of Health of Russia. Phone: +79269381956. E-mail: maria.makarova.work@gmail.com
117997 Russia, GSP-7, Moscow, ul. Profsoyuznaya, 86.
Vlada V. Kometova, candidate of medical sciences, senior researcher of the pathology department of the Federal State Budgetary Institution National Medical Research
Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakova Ministry of Health of Russia. Tel.: +79051837783.
E-mail: vladakometova@gmail.com; https://orcid.org/0000-0001-9666-6875
117997 Russia, Moscow, ul. Academician Oparin, d.4.
Lev A. Ashrafyan, MD Professor, Academician of the Russian Academy of Sciences, Deputy Director of the National Medical Research Center for Obstetrics, Gynecology and Perinatology Academician V.I. Kulakova Ministry of Health of Russia; Director of the Institute of Oncogynecology and Mammology, Federal State Budgetary Institution National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakova Ministry of Health of Russia. Tel.: +79257402745. E-mail: info@oparina4.ru. 117997 Russia, Moscow, ul. Academician Oparin, d.4.

For citation: Dergunova Yu.A., Bozhenko V.K., Podionov V.V., Kometova V.V., Makarova M.V., Ashrafyan L.A. Molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer patients.
Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2020; 3: 141-7. (In Russian).
https://dx.doi.org/10.18565/aig.2020.3.141-147

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