Genetic classification of ovarian carcinoma based on microsatellite analysis: Relationship to clinicopathological features and patient survival

Zhang Huan, Kentaro Nakayama, Naomi Nakayama, Masako Ishibashi, Shamima Yeasmin, Atsuko Katagiri, Indri Nuryani Purwana, Kouji Iida, Riruke Maruyama, Manabu Fukumoto, Kohji Miyazaki

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Ovarian carcinomas can progress through two pathways of genomic instability: chromosomal instability (CIN) and microsatellite instability (MSI). However, it is unknown whether these two mechanisms could be distinguished from each other in the molecular characteristics in ovarian carcinomas. We hypothesized that these two pathways are not always independent in ovarian carcinomas. We classified 51 ovarian carcinomas based on their MSI and CIN status using microsatellite analysis and assessed whether these carcinogenic pathways affect the clinicopathological features and patient survival. Of the 51 cases, 77.4% of the tumors were microsatellite stable (MSS), 5.9% were MSI-Low (MSI-L) whilst, 16.7% were MSI-High (MSI-H). Overall, 56.8% of the tumors had at least one loss of heterozygosity (LOH) event, i.e., 56.8% CIN. Notably, we identified a significant degree of overlap between the MSI and CIN pathways. Of the 34 tumors with LOH events (CIN), 5 (14.7%) were MSI-H. In addition, of the 7 tumors that were MSI-H, 5 (71.4%) had one or more LOH events (CIN). We also identified a group of 29.4% of all tumors that did not demonstrate any evidence of either of the two pathways of genomic instability as they were MSS/MSI-L with no evidence of LOH events (CIN negative). Furthermore, patients with CIN with MSS/ MSI-L have a significantly shorter overall survival compared to those in other genetic categories (P=0.019). Cox regression analysis revealed that tumors with CIN with MSS/MSI-L exhibit a poor prognostic outcome after adjustment for FIGO stage and grade. These findings suggest that some ovarian carcinomas have a significant degree of overlap between the two pathways of genomic instability and that the genetic classification using microsatellite markers may represent a potential new biomarker of risk prediction in ovarian carcinoma.

Original languageEnglish
Pages (from-to)775-781
Number of pages7
JournalOncology reports
Volume19
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Keywords

  • Genomic instability
  • Loss of heterozygosity
  • Microsatellite instability
  • Ovarian carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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