New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.

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UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Cancers ◽

10.3390/cancers10080262 ◽

2018 ◽

Vol 10 (8) ◽

pp. 262 ◽

Cited By ~ 8

Author(s):

Laura Hardy ◽

Amrita Salvi ◽

Joanna Burdette

Keyword(s):

Ovarian Cancer ◽

Fallopian Tube ◽

Cancer Progression ◽

Drug Targets ◽

Ovarian Surface Epithelium ◽

Surface Epithelium ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cell Of Origin ◽

Pax8 Expression

High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

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A mini-review regarding the carcinogenesis and morphology of serous tumors of the ovary, fallopian tube and peritoneum

Journal of Mind and Medical Sciences ◽

10.22543/7674.81.p4452 ◽

2021 ◽

Vol 8 (1) ◽

pp. 44-52

Author(s):

Tiberiu-Augustin Georgescu ◽

Roxana Bohiltea ◽

Octavian Munteanu ◽

Corina Grigoriu ◽

Ioana Paunica ◽

...

Keyword(s):

Fallopian Tube ◽

Female Genital Tract ◽

Molecular Classification ◽

Genetic Alterations ◽

Serous Carcinoma ◽

Low Grade ◽

High Grade ◽

Cancer Pathogenesis ◽

Well Differentiated ◽

Serous Tumors

Similar to the already well-recognized adenoma-carcinoma sequence in colorectal cancer pathogenesis, it has been believed for many decades that the progression of ovarian epithelial tumors occurs from benign serous cystadenomas to borderline tumors, to well-differentiated carcinomas, and ultimately, to poorly differentiated carcinomas. However, it is currently accepted that low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC) are fundamentally different tumor types and, consequently, different diseases. In fact, whereas the benign-borderline-malignant sequence seems to apply quite well to low-grade serous carcinoma, the sequence of genetic alterations in high-grade serous carcinoma is substantially different. In this mini-review, we included the current consensus regarding the morphological and etiopathogenic results regarding serous tumors of the ovary, fallopian tube and peritoneum. It also briefly describes the history of benign, borderline and malignant serous tumors, discussing multiple types of dichotomies in serous carcinomas of the female genital tract and summarizing the current molecular classification.

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550 Novel 3D model systems to assess heterogeneity in response to platinum therapy in high grade serous ovarian cancer

10.1136/ijgc-2020-esgo.172 ◽

2020 ◽

Author(s):

Jennifer Ploski ◽

Katherine Nixon ◽

Nikita Demchenko ◽

Paula Cunnea ◽

Christina Fotopoulou

Keyword(s):

Ovarian Cancer ◽

3D Model ◽

Model Systems ◽

High Grade ◽

Serous Ovarian Cancer

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Differential expression of SLIT and NTRK-like family member 3 in human epithelial ovarian cancer.

10.31219/osf.io/jdrct ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Family Member ◽

Fallopian Tube ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Progression Free Survival ◽

High Grade ◽

Primary Tumors ◽

Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding SLIT and NTRK-like family member 3, SLITRK3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLITRK3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLITRK3 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SLITRK3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLITRK3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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Differential expression of LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated in human epithelial ovarian cancer.

10.31219/osf.io/g42sh ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Fallopian Tube ◽

Expression Profiles ◽

Mrna Degradation ◽

High Grade ◽

Small Nuclear Rna ◽

Primary Tumors ◽

Ovarian Cancers ◽

Nuclear Rna

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated, LSM4, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. LSM4 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. LSM4 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of LSM4 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. LSM4 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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Differential expression of murine retrovirus integration site 1 homolog in human epithelial ovarian cancer.

10.31219/osf.io/ru5e6 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Fallopian Tube ◽

Integration Site ◽

Expression Profiles ◽

Gynecologic Cancer ◽

High Grade ◽

Primary Tumors ◽

Ovarian Cancers ◽

Retrovirus Integration

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding murine retrovirus integration site 1 homolog, MRVI1, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. MRVI1 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. MRVI1 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of MRVI1 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. MRVI1 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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Differential expression of sarcospan in human epithelial ovarian cancer.

10.31219/osf.io/k4ceq ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Fallopian Tube ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Gene Expression Profiles ◽

Progression Free Survival ◽

High Grade ◽

Primary Tumors ◽

Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding sarcospan, SSPN, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SSPN expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SSPN expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SSPN is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SSPN may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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Differential expression of phosphodiesterase 5A in human epithelial ovarian cancer.

10.31219/osf.io/3jkpe ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Fallopian Tube ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Gene Expression Profiles ◽

Progression Free Survival ◽

High Grade ◽

Primary Tumors ◽

Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding phosphodiesterase 5A, PDE5A, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. PDE5A expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. PDE5A expression correlated with progression-free survival in patients with p53 mutant ovarian cancer. These data indicate that expression of PDE5A is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. PDE5A may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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