Prognostic significance of Ki-67 levels and hormone receptor expression in low-grade serous ovarian carcinoma: an investigation of the Tumor Bank Ovarian Cancer Network

Hum Pathol. 2019 Mar:85:299-308. doi: 10.1016/j.humpath.2018.10.020. Epub 2018 Nov 11.

Abstract

Low-grade serous ovarian carcinoma (LGSOC) has recently come up as a distinct rare entity of epithelial ovarian cancer. Predictive and prognostic markers are not well studied yet. Because Ki-67 and hormone receptors (HR) have been established as relevant cancer biomarkers in several malignant tumors, we evaluated Ki-67 and HR expression rates by immunohistochemistry in 68 patients with LGSOC. We used a standardized cutoff finder algorithm to analyze prognostic significance for overall survival (OS) and progression-free survival (PFS). Cox regression showed a significant continuous decrease in OS for higher proliferation rates with an HR of 1.07% (95% confidence interval, 1.01%-3.67%; P = .048) but not in PFS (P = .86). Cutoff finder analysis revealed the best possible cutoff for OS at 6.28% (P = .04) and for PFS at 1.85% proliferative activity (P = .04). Estrogen receptors (ERs) were expressed in most LGSOC patients (n = 61; 89.7%), progesterone receptor (PR) in about half of patients (n = 33; 48.5%). For both ER/PR, a statistically significant cutoff for PFS could be determined, which was at 75% of positive tumor cells for ER (P = .02) and at 15% of positive tumor cells for PR (P = .03). For OS, HR expression showed a tendency toward better OS for HR-positive tumors but did not turn out statistically significant. Our results show that Ki-67 is a valuable prognostic marker in the subgroup of LGSOC. We could also show that most LGSOCs express HRs but that this expression is associated with a better PFS, a finding valuable in times of antihormonal therapy in LGSOC.

Keywords: Hormone receptor; Ki-67; Low-grade serous ovarian carcinoma; Prognostic marker; Proliferative activity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Progression-Free Survival
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone