Analysis of Clinicopathologic Factors and KRAS Gene Mutation in Epithelial Ovarian Cancer Outcomes

Andi  Friadi; Wirsma Arif Harahap; Arni Amir; Andri Andrijono

doi:10.3889/oamjms.2020.5147

Authors

Andi Friadi Department of Obstetrics and Gynecology, Faculty of Medicine, Andalas University, Padang, Indonesia
Wirsma Arif Harahap Department of Surgery, Faculty of Medicine, Andalas University, Padang, Indonesia
Arni Amir Department of Biology, Faculty of Medicine, Andalas University, Padang, Indonesia
Andri Andrijono Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.5147

Keywords:

Ovarian cancer, Cancer staging, KRAS mutation, Survival

Abstract

BACKGROUND: Raise of ovarian cancer mortality is caused by high ovarian cancer recurrence. This is related to many prognostic factors. Kirsten-rat sarcoma virus oncogene (KRAS) is a proto-oncogene that regulates proliferation, growth and cell motility. The controversy of some experts regarding KRAS mutations in the prognosis of ovarian cancer makes it interesting to analyze.

AIM: The aim of this study is to clarify whether the clinicopathologic factors and KRAS gene mutation affect the recurrence of patients with ovarian cancer in Indonesia.

METHODS: The authors conducted a retrospective cohort study. Clinicopathological factors and prognoses were obtained for 205 patients who were histopathologically diagnosed with epithelial ovarian cancer or ovarian borderline malignant tumor, operated from June 2015 to January 2019 at Dr. M. Djamil General Hospital. We gathered 80 patients who were diagnosed with epithelial ovarian cancer since June 2015 until January 2019. These cases were analyzed after 2-year follow-up or recurrence occurred. Survival rate was determined using the Kaplan–Meier method and examined by Log rank test. All analyses were performed using STATA ver. 12.0, with p < 0.05 considered to be significant.

RESULTS: Among KRAS mutation group, the 2-year disease free survival rate (2y-DFS) was 31.56% and 47.58% in non-mutation group with significant differences between mutation and non-mutation (p = 0.02). There was a significant difference between early stage ovarian cancer with non-mutation group and advanced stages ovarian cancer with mutation group (p = 0.00). Among combination staging with mutation group, the 2y-DFS was 85.79% in early stage ovarian cancer with non-mutation, 44.44% in early stage with mutation, 10.65% in advanced stage with non-mutation, and 20.00% in advanced stage with mutation.

CONCLUSION: The results suggest that staging and KRAS mutation are the most influence prognostic factors for epithelial ovarian cancer. There was a discrepancy of prognosis by staging and mutation between early stage with non-mutation and advanced stage with KRAS mutation.

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References

Rankin EB. Genomics and molecular mechanisms of high grade serous ovarian cancer: The 12th biennial rivkin center ovarian cancer research symposium. Int J Gynecol Cancer. 2019;29(2):S7-11. https://doi.org/10.1136/ijgc-2019-000490 PMid:31462542

Erol A, Niemira M, Kretowski AJ. Novel approaches in ovarian cancer research against heterogeneity, late diagnosis, drug resistance, and transcoelomic metastases. Int J Mol Sci. 2019;20(11):2649. https://doi.org/10.3390/ijms20112649 PMid:31146417

Carta C, Pantaleoni F, Bocchinfuso G, Stella L, Vasta I, Sarkozy A, et al. Germline missense mutations affecting KRAS Isoform B are associated with a severe noonan syndrome phenotype. Am J Hum Genet. 2006;79(1):129-35. https://doi. org/10.1086/504394 PMid:16773572

Murugan AK, Grieco M, Tsuchida N. RAS mutations in human cancers: Roles in precision medicine. Semin Cancer Biol. 2019;59:23-35. https://doi.org/10.1016/j. semcancer.2019.06.007 PMid:31255772

Hobbs GA, Der CJ. RAS mutations are not created equal. Cancer Discov. 2019;9(6):696-8. https://doi.org/10.1158/2159- 8290.cd-19-0406 PMid:31160330

Khurana E, Fu Y, Chakravarty D, Demichelis F, Rubin MA, Gerstein M. Role of non-coding sequence variants in cancer. Nat Rev Genet. 2016;17:93-108. https://doi.org/10.1038/ nrg.2015.17 PMid:26781813

Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagn Pathol. 2013;8:106. https://doi. org/10.1186/1746-1596-8-106 PMid:23800114

Zhou H, Dai Y, Zhu L, Wang C, Fei X, Pan Q, et al. Poor response to platinum-based chemotherapy is associated with KRAS mutation and concomitant low expression of BRAC1 and TYMS in NSCLC. J Int Med Res. 2016;44:89-98. https://doi. org/10.1177/0300060515607383 PMid:26740498

Pavlik EJ, Smith C, Dennis TS, Harvey E, Huang B, Chen Q, et al. Disease-specific survival of Type I and Type II epithelial ovarian cancers-stage challenges categorical assignments of indolence and aggressiveness. Diagnostics (Basel). 2020;10(2):56. https://doi.org/10.3390/diagnostics10020056 PMid:31973035

Prat J. Ovarian, fallopian tube and peritoneal cancer staging: Rationale and explanation of new FIGO staging 2013. Best Pract Res Clin Obstet Gynaecol. 2015;29(6):858-69. https://doi. org/10.1016/j.bpobgyn.2015.03.006 PMid:25890882