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Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors.

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.

SUBMITTER: Barone A

PROVIDER: S-EPMC7539041 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors.

Barone Angela A Linder Anna A Mateoiu Constantina C Köster Larsen Rasmus R Blixt Ola O Teneberg Susann S Sundfeldt Karin K

Frontiers in oncology 20200923

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-Lc<sub>4</sub>) was characterized in two out of three cases. The presence and level of S-Lc<sub>4</sub> was further evaluated immunohistochemically in a ...[more]

PMID: 33072588

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Project description:BackgroundEpithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancer cell lines and tumors, including representatives of three major histologies.Methodology/principal findingsWe obtained DNA methylation profiles of 1,505 CpG sites (808 genes) in 27 primary epithelial ovarian tumors and 15 ovarian cancer cell lines. We found that the DNA methylation profiles of ovarian cancer cell lines were markedly different from those of primary ovarian tumors. Aggregate DNA methylation levels of the assayed CpG sites tended to be higher in ovarian cancer cell lines relative to ovarian tumors. Within the primary tumors, those of the same histological type were more alike in their methylation profiles than those of different subtypes. Supervised analyses identified 90 CpG sites (68 genes) that exhibited 'subtype-specific' DNA methylation patterns (FDR<1%) among the tumors. In ovarian cancer cell lines, we estimated that for at least 27% of analyzed autosomal CpG sites, increases in methylation were accompanied by decreases in transcription of the associated gene.SignificanceThe significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies. These data provide a useful resource for future studies, including those of potential tumor progenitor cells, which may help illuminate the etiology and natural history of these cancers.

Dataset Information

Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors.

Publications

Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors.

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