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Association between the expression of GSTP1 and mutant p53, poor chemotherapy response and metastasis in patients
Bangkit Primayudha1,2, Evelina Kodrat3, Yogi Prabowo1
1Department of Orthopedic and Traumatology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo General Hospital, Central Jakarta 10430, Indonesia.
Abstract:
Osteosarcoma, a primary malignant tumor of the bone, is known for its aggressive behavior and tendency to metastasize to the lungs. The standard treatment for osteosarcoma includes surgery combined with chemotherapy. However, genetic changes and chromosomal contributions influence the tumor's aggressive behavior and influence the effectiveness of chemotherapy, often resulting in drug resistance and metastasis. The present study aimed to assess the association between increased expression of mutant p53 and glutathione S-transferase P1 (GSTP1), poor chemotherapy response and the occurrence of metastasis in patients with osteosarcoma. The study is a cross-sectional study using paraffin blocks retrieved from the Department of Anatomical Pathology at Cipto Mangunkusumo Hospital (Jakarta, Indonesia) containing tissues gathered from patients diagnosed with osteosarcoma who received the first-line drug of neoadjuvant chemotherapy for three cycles from January 2019 to December 2021. Immunohistochemical examinations of GSTP1 and mutant p53 were conducted, using the Fedchenko and Reifenrath immunoreactive scoring system. The results obtained after the immunohistochemical examination and evaluation of GSTP1 expression and mutant p53 expression were subjected to bivariate association analysis with chemotherapy response (Huvos Score) and the occurrence of metastasis. This study involved a total of 36 patients. Statistical analysis using the Fisher's exact test revealed a significant association between increased GSTP1 expression and a poor chemotherapy response, as well as between increased mutant P53 expression and a poor chemotherapy response. By contrast, no significant association was found between GSTP1 or mutant P53 expression and the occurrence of metastasis. In conclusion, a significant association was found between the increasing expression levels of GSTP1 and mutant p53 and a poor chemotherapy response in patients with osteosarcoma, while no significant association was found between the increasing expression of GSTP1 and mutant p53 and the occurrence of metastasis in these patients.