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Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Analysis of hMLH1 and hMSH2 expression in cisplatin-treated ovarian cancer patients
Magdalena Magnowska1, Paweł Surowiak, Ewa Nowak-Markwitz
1Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, Polna.
Background:
Loss of DNA mismatch repair may result in resistance to platinum- based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the maintenance of genome integrity and are involved in resistance to platinum-based therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined.
Objective:
The aim of this study was to investigate the expression of hMLH1 and hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic significance by means of overall survival (OS) and progression-free survival rates (PSF).
Material:
Ovarian cancer tissues were obtained from 61 patients: 45 platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression was evaluated by immunohistochemistry, with the use of mouse monoclonal antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and Kaplan-Meier statistics were used to analyze the relationship between proteins expression and progression free survival, as well as the overall survival.
Result:
No significant correlation was found between hMLH1 and hMSH2 expression and overall survival and progression free survival in the group of patients sensitive and resistant to cisplatin. No significant difference was found in proteins expression intensity between the two compared groups of patients. Age of patients, type of cancer histology, FIGO staging, grading, clinical response and CA 125 did not reveal correlation with the expression of the analyzed proteins.
Conclusion:
The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.
Insights
The expression of hMLH1 and hMSH2 proteins does not predict cisplatin resistance in ovarian cancer. Further research is needed to identify reliable biomarkers for platinum-based chemotherapy response.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA mismatch repair (MMR) deficiency, involving hMLH1 and hMSH2 proteins, is linked to platinum-based anticancer drug resistance.
- While established in colorectal and endometrial cancers, the predictive role of MLH1 and MSH2 in ovarian cancer cisplatin resistance remains unclear.
Purpose of the Study:
- To investigate hMLH1 and hMSH2 protein expression in ovarian carcinoma.
- To evaluate the prognostic significance of these proteins concerning overall survival (OS) and progression-free survival (PFS).
Main Methods:
- Immunohistochemistry was used to assess hMLH1 and hMSH2 protein expression in 61 ovarian cancer patients (45 platinum-sensitive, 16 platinum-resistant).
- Log-rank test and Kaplan-Meier statistics analyzed the correlation between protein expression and survival outcomes.
Main Results:
- No significant correlation was found between hMLH1/hMSH2 expression and OS or PFS in cisplatin-sensitive or resistant ovarian cancer patients.
- Protein expression intensity did not differ significantly between sensitive and resistant groups.
- Patient age, histology, FIGO stage, grading, clinical response, and CA 125 levels showed no correlation with analyzed protein expression.
Conclusions:
- Immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer lacks predictive value for cisplatin resistance.
- These proteins are not reliable biomarkers for predicting response to platinum-based chemotherapy in ovarian cancer.
