Abstract
Ovarian carcinoma is a heterogeneous disease with distinct molecular and histological profiles, ranging from low grade atypia to highly aggressive tumors associated with a poor prognosis. In the present study, glycosphingolipids were isolated from human high-grade serous ovarian carcinoma, whereby the novel stem cell marker Sialyl-lactotetra (S-Lc4) was characterized in two out of three cases. The presence and level of S-Lc4 was further evaluated immunohistochemically in a cohort of patients with ovarian tumors ranging from benign lesions to high grade serous carcinoma (n = 478). Its expression was assessed in association with tumor grade, stage, histology, and survival. The data showed that S-Lc4 is most common and highly expressed in borderline type tumors and carcinomas with low levels of aggressiveness, such as mucinous, endometrioid, and low grade serous. Accordingly, S-Lc4-positivity was associated with better disease-free survival. The expression of S-Lc4 was seemingly associated with lineage continuity and could be traced from premalignant lesions to carcinoma, suggesting inheritance by a stem cell lineage that gives rise to generally indolent tumors.
Highlights
Ovarian carcinoma is the most lethal gynecological cancer [1]
We have evaluated the potential of S-Lc4 as a biomarker for ovarian tumors, by isolation and characterizing glycosphingolipids from three human High-grade serous carcinoma (HGSC), and examination of the immunoreactivity of anti-S-Lc4 antibodies in a comprehensive tissue micro array of benign, borderline type and malignant ovarian tumor samples
To determine whether SLc4 is expressed in ovarian carcinomas, acid and non-acid glycosphingolipids were isolated from three cases of HGSC by standard methods
Summary
Ovarian carcinoma is the most lethal gynecological cancer [1]. The high mortality is mainly associated with late discovery due to vague symptoms [2] and the high prevalence of recurrence [3]. Recurrence is believed to be associated with the inability to eradicate the entire original tumor burden, and the presence of cancer cells in the residual tissue with stem-like properties that serve as ancestries of drug resistance and recurrent disease [5, 6]. It has been suggested that the cell surface markers used for definition and characterization of human pluripotent stem cells may serve as markers for cancer detection or as targets of cancer therapy [7]. Many such stem cell markers are based on cell surface carbohydrate epitopes, such as the widely used glycosphingolipids globopentaosylceramide/SSEA-3 and sialylglobopentaosylceramide/SSEA-4, and the glycoprotein TRA 1-60/TRA 1-81 markers [8]
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