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.
Highlights
Ovarian cancer, consisting predominantly of ovarian carcinoma (OC), constitutes the 8th most common cancer and the 8th most common cause of cancer death in women globally, with 295,414 new diagnoses and 184,799 deaths in 2018 [1]
We studied the clinical role of the cancer stem cell (CSC) marker SSEA1 in a large cohort of patients with high-grade serous carcinoma (HGSC) effusions, the majority diagnosed at FIGO stages III–IV
As Nanog, SOX2, and Oct3/4 were previously studied in our cohort [10], and given the fact that Stage-specific embryonic antigen 4 (SSEA4) expression by flow cytometry (FCM) was low, we expanded the study with respect to SSEA1, analyzing a large series of HGSC effusions
Summary
Ovarian cancer, consisting predominantly of ovarian carcinoma (OC), constitutes the 8th most common cancer and the 8th most common cause of cancer death in women globally, with 295,414 new diagnoses and 184,799 deaths in 2018 [1]. Despite improvement in survival in recent years, due to optimized surgery and chemotherapy protocols, as well as targeted therapy, 5-year survival is only 45%. This figure is true for all histological types combined, and outcome is still worse for patients diagnosed with high-grade serous carcinoma (HGSC), the most common and aggressive type of OC, in which. Molecules that have been reported to be cancer stem cell (CSC) markers in OC include the surface proteins CD24, CD44, CD117, and CD133, and the intracellular cytoplasmic and/or nuclear proteins aldehyde dehydrogenase isoform 1A1 (ALDH1A1), OCT4, Nanog, SOX2, Notch-1, and nestin, as well as the detection of a side population by flow cytometry (FCM) [reviewed in 3, 4] The majority of these markers have been shown to be expressed in OC cells in effusions, an anatomic niche characterized by anoikis resistance and chemoresistance [reviewed in 5–7]
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