GSTM1, GSTP1, p53 as some probable predictors of prognosis in primary and metastatic epithelial ovarian cancer

Abstract

Objectives: Ovarian carcinomas are responsible for the death of more women than all other gynecologic malignancies in the Western world. Ovarian carcinomas are detected in an advanced stage of the disease in approximately 80% of the patients. Glutathione S-transferases (GSTs) are an important family involved in the detoxification of several xenobiotics. Thus, this mechanism protects tissues from the harmful effects of oxidative stress and chemical-induced damages. The expression of them may contribute to the characteristics of ovarian carcinoma as they can metabolise both exogenous and endogenous compounds, which are implicated in the development of ovarian cancer. Therefore, our aim was to determine the expressions of GST Mu 1 (GSTM1), GST Pi 1 (GSTP1), and also p53, which is a tumor suppressor gene, in benign and malign ovarian tumors and metastasis tissues.

Methods: A total of the 99 patients with ovarian tumor enrolled in the study. Thirty-one of the tissues was benign tumor, 17 was malign tumor and 51 was metastasis. The immunohistochemical GSTM1, GSTP1, and p53 staining characteristics of these tissues were investigated.

Results: The highest GSTM1, GSTP1, and p53 expression was noted in the malignant group followed by the metastasis group. GSTP1 expression was significantly higher in malignant tissues than benign ones (p = 0.015). No statistically significant difference was observed in the level of GSTM1 expression between groups (p = 0.524). p53 expression was significantly higher in the metastasis and malignant tissues than the benign ones (p < 0.001).

Conclusions: The higher expressions of GSTP1 and p53 in malignant and metastasis tissues than benign ones indicate that these expressions could be important biomarkers in ovarian cancer development and progression. Further studies with more cases are required to confirm the results of our present study.

Keywords

• Ovary carcinoma
• glutathione-S-transferase
• p53
• immunohistochemistry

References

1. 1. Edmondson RJ, Monaghan JM. The epidemiology of ovarian cancer. Int J Gynecol Cancer 2001;11:423-9.
2. 2. Chu CS, Rubin SC. Screening for ovarian cancer in the general population. Best Pract Res Clin Obstet Gynaecol 2006;20:307-20.
3. 3. American Cancer Society, Ovarian Cancer, Global Cancer Fact & Figures American Cancer Society, Atlanta, GA, USA. 2011.
4. 4. Donald PJ. Marijuana smoking -- possible cause of head and neck carcinoma in young patients. Otolaryngol Head Neck Surg 1986;94:517-21.
5. 5. Guengerich FP. Characterization of human microsomal cytochrome P-450 enzymes. Ann Rev Pharmacol Toxicol 1989;29:241-64.
6. 6. Caldwell J. Conjugation reactions in foreign-compound metabolism: definition, consequences, and species variations. Drug Metab Rev 1982;13:745-77.
7. 7. Board P, Coggan M, Johnston P, Ross V, Suzuki T, Webb G. Genetic heterogeneity of the human glutathione transferases: a complex of gene families. Pharmacol Ther 1990;48:357-69.
8. 8. Commandeur JN, Stijntjes GJ, Vermeulen NP. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of xenobiotics. Pharmacol Rev 1995;47:271-330.

9. 9. Di Pietro G, Magno LA, Rios-Santos F. Glutathione S-transferases: an overview in cancer research. Expert Opin Drug Metab Toxicol 2010;6:153-70.
10. 10. Moscow JA, Fairchild CR, Madden MJ, Ransom DT, Wieand HS, O'Brien EE, et al. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res 1989;49:1422-8.
11. 11. Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev 1996;10:1054-72.
12. 12. Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes Dev 1990;4:1-8.
13. 13. Maity A, McKenna WG, Muschel RJ. The molecular basis for cell cycle delays following ionizing radiation: a review. Radiother Oncol 1994;31:1-13.
14. 14. Kupryjańczyk J, Thor AD, Beauchamp R, Merritt V, Edgerton SM, Bell DA, et al. p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci U S A 1993;90:4961-5.
15. 15. Cui J, Li G, Yin J, Li L, Tan Y, Wei H, et al. GSTP1 and cancer: expression, methylation, polymorphisms and signaling (Review). Int J Oncol 2020;56:867-78.
16. 16. Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 1991;51:2979-84.
17. 17. Green JA, Robertson LJ, Clark AH. Glutathione S-transferase expression in benign and malignant ovarian tumours. Br J Cancer 1993;68:235-9.
18. 18. Baxter SW, Thomas EJ, Campbell IG. GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer. Carcinogenesis 2001;22:63-6.
19. 19. Howells REJ, Holland T, Dhar KK, Redman CWE, Hand P, Hoban PR, et al. Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival. Int J Gynecol Cancer 2001;11:107-12.
20. 20. Oliveira C, Lourenco GJ, Sagarra RAM, Derchain SFM, Segalla JG, Lima CSP. Polymorphisms of glutathione S-transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) genes and epithelial ovarian cancer risk. Dis Markers 2012;33:155-9.