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Features of the expression of the molecular chaperones Hsp27 and Hsp90 in serous ovarian cancer
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Introduction. Ovarian cancer (OC) represents the second most common cause of death from gynecologic cancer, with serous cancer being the most common and aggressive of all histologic variants. The search for new biomarkers and therapeutic targets for the OC treatment is an urgent task of gynecologic oncology. In recent years, researchers have focused their attention on the study of heat shock proteins (Hsps), which are molecular chaperones synthesized in response to stress factors exposure and contributing to the refolding of damaged proteins and restoring their cellular functions. Molecular chaperones are involved in maintaining cell homeostasis, regulating the activity of oncogenes and tumor suppressors.
Aim. To study the features of the Hsp27 and Hsp90 expression in serous OC compared with borderline ovarian tumors, taking into account the intracellular localization and the potential diagnostic value of these markers.
Materials and methods. The study included 23 patients with newly diagnosed serous OC and 6 women with FIGO stage I–IIIC borderline ovarian tumors (mean age 53,4 ± 8,1 years) who were treated at the Tomsk Research Institute of Oncology and/or Tomsk Regional Oncological Center. The study objects were paraffin blocks from tumor tissue obtained during biopsy and surgery intervention during laparoscopic surgical staging before the treatment. The intracellular localization of Hsp27 and Hsp90 in tumor and stromal cells was determined by immunohistochemical (IHC) staining.
Results. The IHC study revealed that the expression of Hsp27 in tumor cells, when calculated by cytoplasm and nucleus, is 10,48 and 7,41 times higher than in the stroma, respectively; the expression of Hsp90 in tumor cells is 40,42 and 86,67 times higher in cytoplasm and nuclei than in stromal cells, respectively. The count of Hsp27-positive tumor cells is 3,2 times higher than the count of Hsp90-positive tumor cells in tissue of ovarian serous adenocarcinoma (p = 0,0006, Wilcoxon test). In borderline ovarian tumors, the count of Hsp27- and Hsp90-positive tumor cells is significantly lower than in OC (p < 0,0001 and p = 0,0018, respectively, Mann-Whitney test).
Conclusion. The significant difference in the expression of the molecular chaperones Hsp27 and Hsp90 in the cellular compartments of tumor and stromal cells, as well as a more than fourfold increase in this marker in serous ovarian carcinoma compared with borderline tumors show the diagnostic and prognostic role of Hsp27 and Hsp90 in the immunohistochemical diagnosis of OC, as well as the prospects of Hsp27 and Hsp90 activity modulation targeted therapy.
FSBEI HE NSMU MOH Russia
Title: Features of the expression of the molecular chaperones Hsp27 and Hsp90 in serous ovarian cancer
Description:
Introduction.
Ovarian cancer (OC) represents the second most common cause of death from gynecologic cancer, with serous cancer being the most common and aggressive of all histologic variants.
The search for new biomarkers and therapeutic targets for the OC treatment is an urgent task of gynecologic oncology.
In recent years, researchers have focused their attention on the study of heat shock proteins (Hsps), which are molecular chaperones synthesized in response to stress factors exposure and contributing to the refolding of damaged proteins and restoring their cellular functions.
Molecular chaperones are involved in maintaining cell homeostasis, regulating the activity of oncogenes and tumor suppressors.
Aim.
To study the features of the Hsp27 and Hsp90 expression in serous OC compared with borderline ovarian tumors, taking into account the intracellular localization and the potential diagnostic value of these markers.
Materials and methods.
The study included 23 patients with newly diagnosed serous OC and 6 women with FIGO stage I–IIIC borderline ovarian tumors (mean age 53,4 ± 8,1 years) who were treated at the Tomsk Research Institute of Oncology and/or Tomsk Regional Oncological Center.
The study objects were paraffin blocks from tumor tissue obtained during biopsy and surgery intervention during laparoscopic surgical staging before the treatment.
The intracellular localization of Hsp27 and Hsp90 in tumor and stromal cells was determined by immunohistochemical (IHC) staining.
Results.
The IHC study revealed that the expression of Hsp27 in tumor cells, when calculated by cytoplasm and nucleus, is 10,48 and 7,41 times higher than in the stroma, respectively; the expression of Hsp90 in tumor cells is 40,42 and 86,67 times higher in cytoplasm and nuclei than in stromal cells, respectively.
The count of Hsp27-positive tumor cells is 3,2 times higher than the count of Hsp90-positive tumor cells in tissue of ovarian serous adenocarcinoma (p = 0,0006, Wilcoxon test).
In borderline ovarian tumors, the count of Hsp27- and Hsp90-positive tumor cells is significantly lower than in OC (p < 0,0001 and p = 0,0018, respectively, Mann-Whitney test).
Conclusion.
The significant difference in the expression of the molecular chaperones Hsp27 and Hsp90 in the cellular compartments of tumor and stromal cells, as well as a more than fourfold increase in this marker in serous ovarian carcinoma compared with borderline tumors show the diagnostic and prognostic role of Hsp27 and Hsp90 in the immunohistochemical diagnosis of OC, as well as the prospects of Hsp27 and Hsp90 activity modulation targeted therapy.
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