Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcino
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ORIGINAL ARTICLE
Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma Ben Davidson 1,2
&
Arild Holth 1 & Hiep Phuc Dong 1
Received: 23 April 2020 / Revised: 12 May 2020 / Accepted: 18 May 2020 # The Author(s) 2020
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 . SSEA1 . Immunohistochemistry . Flow cytometry . High-grade serous carcinoma . Effusion
Introduction 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%. Furthermore, 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
* Ben Davidson [email protected] 1
Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway
2
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway
diagnosis is often at advanced stage (FIGO stages III–IV) and death-of-disease occurs within 5 years in the majority of patients [2]. HGSC has its origin most frequently in the fallopian tube, and metastasizes widely within the
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