Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs

The aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Mater...

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Main Authors: G. V. Zhukova, E. P. Ulyanova, A. P. Menshenina, T. I. Moiseenko, E. Yu. Zlatnik, E. M. Nepomnyashchaya, A. B. Sagakyants, E. V. Verenikina
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2024-09-01
Series:Сибирский онкологический журнал
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Online Access:https://www.siboncoj.ru/jour/article/view/3191
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author G. V. Zhukova
E. P. Ulyanova
A. P. Menshenina
T. I. Moiseenko
E. Yu. Zlatnik
E. M. Nepomnyashchaya
A. B. Sagakyants
E. V. Verenikina
author_facet G. V. Zhukova
E. P. Ulyanova
A. P. Menshenina
T. I. Moiseenko
E. Yu. Zlatnik
E. M. Nepomnyashchaya
A. B. Sagakyants
E. V. Verenikina
author_sort G. V. Zhukova
collection DOAJ
description The aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Material and Methods. An immunohistochemical study of tumor tissue was carried out in patients with high-grade serous ovarian cancer (stage IIIC–IV). The age of the patients ranged from 49–72 years. There were 59 patients who were sensitive and 22 patients who were resistant to platinum-containing adjuvant polychemotherapy. In the tissue of ovarian tumors obtained during surgery after noadjuvant polychemotherapy, we studied immunohistochemical indicators of proliferative activity (Ki67), expression of the DNA excision repair protein ERCC1 and proteins of the ABC transporter family – Pgp and BCRP, as well as statistical relationships between these indicators (Spearman’s rank correlation coefficient). Results. After effective neoadjuvant polychemotherapy, more pronounced signs of activity in the processes of proliferation, DNA repair and xenobiotic efflux were noted in serous ovarian carcinomas, which subsequently demonstrated resistance to platinum-containing polychemotherapy regimens compared to tumors that retained platinum sensitivity. Moreover, in 40 % of cases or more, there was a coincidence in the ranges of values of the studied parameters in tumors with different sensitivity to platinum drugs. The expression of transporter proteins greater than 60 % for BCRP and 65 % for Pgp was shown to precede the development of resistance to adjuvant treatment with carboplatin. In the studied groups, differences in the number and significance of statistical relationships between the variables were observed. The most significant differences were noted for the Ki67 – BCRP correlation, which had the opposite direction in groups with different sensitivity to adjuvant treatment with carboplatin. Conclusion. A comprehensive immunohistochemical analysis of highgrade serous ovarian carcinomas after neoadjuvant polychemotherapy, which further demonstrated different sensitivity to platinum-containing adjuvant regimens, was carried out, and the prognostic value of the studied parameters was assessed. The revealed critical levels of Pgp and BCRP expression in tumor tissue may have a prognostic value regarding the effect of adjuvant polychemotherapy. The results of the correlation analysis suggest a relationship between the development of platinum resistance and changes in the nature of the regulatory relationships between proliferative activity and transport processes in tumor tissue.
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spelling doaj-art-16577991c9404cefa3d2b666045ff7b72025-08-20T02:55:49ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682024-09-01234455310.21294/1814-4861-2024-23-4-45-531251Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugsG. V. Zhukova0E. P. Ulyanova1A. P. Menshenina2T. I. Moiseenko3E. Yu. Zlatnik4E. M. Nepomnyashchaya5A. B. Sagakyants6E. V. Verenikina7National Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaNational Medical Research Center for Oncology of the Ministry of Health of RussiaThe aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Material and Methods. An immunohistochemical study of tumor tissue was carried out in patients with high-grade serous ovarian cancer (stage IIIC–IV). The age of the patients ranged from 49–72 years. There were 59 patients who were sensitive and 22 patients who were resistant to platinum-containing adjuvant polychemotherapy. In the tissue of ovarian tumors obtained during surgery after noadjuvant polychemotherapy, we studied immunohistochemical indicators of proliferative activity (Ki67), expression of the DNA excision repair protein ERCC1 and proteins of the ABC transporter family – Pgp and BCRP, as well as statistical relationships between these indicators (Spearman’s rank correlation coefficient). Results. After effective neoadjuvant polychemotherapy, more pronounced signs of activity in the processes of proliferation, DNA repair and xenobiotic efflux were noted in serous ovarian carcinomas, which subsequently demonstrated resistance to platinum-containing polychemotherapy regimens compared to tumors that retained platinum sensitivity. Moreover, in 40 % of cases or more, there was a coincidence in the ranges of values of the studied parameters in tumors with different sensitivity to platinum drugs. The expression of transporter proteins greater than 60 % for BCRP and 65 % for Pgp was shown to precede the development of resistance to adjuvant treatment with carboplatin. In the studied groups, differences in the number and significance of statistical relationships between the variables were observed. The most significant differences were noted for the Ki67 – BCRP correlation, which had the opposite direction in groups with different sensitivity to adjuvant treatment with carboplatin. Conclusion. A comprehensive immunohistochemical analysis of highgrade serous ovarian carcinomas after neoadjuvant polychemotherapy, which further demonstrated different sensitivity to platinum-containing adjuvant regimens, was carried out, and the prognostic value of the studied parameters was assessed. The revealed critical levels of Pgp and BCRP expression in tumor tissue may have a prognostic value regarding the effect of adjuvant polychemotherapy. The results of the correlation analysis suggest a relationship between the development of platinum resistance and changes in the nature of the regulatory relationships between proliferative activity and transport processes in tumor tissue.https://www.siboncoj.ru/jour/article/view/3191high-grade serous ovarian cancerplatinum resistanceproliferationtransport proteinsstatistical relationshipbiofeedback
spellingShingle G. V. Zhukova
E. P. Ulyanova
A. P. Menshenina
T. I. Moiseenko
E. Yu. Zlatnik
E. M. Nepomnyashchaya
A. B. Sagakyants
E. V. Verenikina
Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
Сибирский онкологический журнал
high-grade serous ovarian cancer
platinum resistance
proliferation
transport proteins
statistical relationship
biofeedback
title Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
title_full Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
title_fullStr Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
title_full_unstemmed Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
title_short Immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum-based drugs
title_sort immunohistochemical parameters of serous ovarian carcinomas and possible mechanism of development of resistance to platinum based drugs
topic high-grade serous ovarian cancer
platinum resistance
proliferation
transport proteins
statistical relationship
biofeedback
url https://www.siboncoj.ru/jour/article/view/3191
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AT apmenshenina immunohistochemicalparametersofserousovariancarcinomasandpossiblemechanismofdevelopmentofresistancetoplatinumbaseddrugs
AT timoiseenko immunohistochemicalparametersofserousovariancarcinomasandpossiblemechanismofdevelopmentofresistancetoplatinumbaseddrugs
AT eyuzlatnik immunohistochemicalparametersofserousovariancarcinomasandpossiblemechanismofdevelopmentofresistancetoplatinumbaseddrugs
AT emnepomnyashchaya immunohistochemicalparametersofserousovariancarcinomasandpossiblemechanismofdevelopmentofresistancetoplatinumbaseddrugs
AT absagakyants immunohistochemicalparametersofserousovariancarcinomasandpossiblemechanismofdevelopmentofresistancetoplatinumbaseddrugs
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