Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma

Virchows Arch. 2020 Nov;477(5):677-685. doi: 10.1007/s00428-020-02850-4. Epub 2020 May 29.

Abstract

The objective of the present study was to perform a quantitative analysis of cancer stem cell (CSC) marker expression in ovarian carcinoma effusions. The clinical role of SSEA1 in metastatic high-grade serous carcinoma (HGSC) was additionally analyzed. CD133, Nanog, SOX2, Oct3/4, SSEA1, and SSEA4 protein expressions were quantitatively analyzed using flow cytometry (FCM) in 24 effusions. SSEA1 expression by immunohistochemistry was analyzed in 384 HGSC effusions. Highly variable expression of CSC markers by FCM was observed, ranging from 0 to 78% of Ber-EP4-positive cells in the case of CD133, with the largest number of negative specimens seen for SSEA4. SSEA1 expression by immunohistochemistry was found in HGSC cells in 336/384 (89%) effusions, most commonly focally (< 5% of cells). SSEA1 was overexpressed in post-chemotherapy disease recurrence specimens compared with chemo-naïve HGSC effusions tapped at diagnosis (p = 0.029). In univariate survival analysis, higher SSEA1 expression was significantly associated with poor overall survival (p = 0.047) and progression-free survival (p = 0.018), though it failed to retain its prognostic role in Cox multivariate survival analysis in which it was analyzed with clinical parameters (p = 0.059 and p = 0.111 for overall and progression-free survival, respectively). In conclusion, CSC markers are variably expressed in ovarian carcinoma effusions. SSEA1 expression is associated with disease progression and poor survival in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

Keywords: Cancer stem cells; Effusion; Flow cytometry; High-grade serous carcinoma; Immunohistochemistry; SSEA1.

MeSH terms

  • AC133 Antigen / analysis
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Flow Cytometry
  • Fucosyltransferases / analysis*
  • Humans
  • Immunohistochemistry
  • Lewis X Antigen / analysis*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Neoplasms, Cystic, Mucinous, and Serous / enzymology*
  • Neoplasms, Cystic, Mucinous, and Serous / mortality
  • Neoplasms, Cystic, Mucinous, and Serous / secondary
  • Neoplasms, Cystic, Mucinous, and Serous / therapy
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / pathology
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Predictive Value of Tests
  • Progression-Free Survival
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Young Adult

Substances

  • AC133 Antigen
  • Lewis X Antigen
  • PROM1 protein, human
  • FUT4 protein, human
  • Fucosyltransferases