The Endometriotic Tumor Microenvironment in Ovarian Cancer

Wendel, Jillian R. H.; Wang, Xiyin; Hawkins, Shannon M.

doi:10.3390/cancers10080261

Cited by 44 publications

(36 citation statements)

References 205 publications

(268 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ovarian cancer is initially associated with pelvic inflammatory disease, such as endometriosis, demonstrating a similarity between the processes of inflammation and carcinogenesis. Endometriotic cells adapt to survive in the unique microenvironment conditions with high levels of iron, inflammatory cytokines and chemokines (98). Microenvironment-cell interplay may modulate the major signaling pathways associated with cell cycle regulation, growth factor signaling, immune and inflammatory pathways, and the extracellular matrix remodeling, which results in phenotype transformation (99).…”

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

View full text Add to dashboard Cite

In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has diseasespecific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

show abstract

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In this study, high expression of MACC1 mRNA in endometrioid cancer patients was significantly associated with unfavorable OS, although PFS did not show statistically significant results. Recently, the interest in carcinogenesis of endometrioid or clear cell carcinoma associated with endometriosis has been increasing [ 26 ]. However, this study was limited in the number of endometrioid cancer cases to produce definite conclusions.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Characteristics of MACC1 Expression in Epithelial Ovarian Cancer

Jeong

Jung

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Recent studies have shown that overexpression of metastasis-associated in colon cancer 1 (MACC1) is significantly associated with adverse prognoses of patients with different kinds of cancer. However, the exact survival effect of MACC1 on epithelial ovarian cancer (EOC) patients has not yet been established. Thus, the objective of this study was to explore the prognostic role of MACC1 mRNA in EOC by using Kaplan-Meier (KM) plotter and ONCOMINE database. Our results indicated that MACC1 mRNA high expression was significantly associated with unfavorable overall survival (hazard ratio (HR) = 1.51 (95% confidence interval (CI): 1.21 – 1.88), P = 0.00025) and progression-free survival (HR = 1.53 (95% CI: 1.24 – 1.89), P = 5.8e-05) in EOC patients. We also found that the expression of MACC1 mRNA in EOC was 2.5 times higher than that in normal surface ovarian epithelium, which was statistically significant (P = 2.86e-7). Our results suggest that MACC1 expression might be a biomarker for poor prognosis in individual EOC patients.

show abstract

“…In general, both clear cell and endometrioid OCs commonly display highly frequent mutations in ARID1A, CTNNB1, KRAS, PIK3CA and PTEN, irrespective of associated endometriosis [156]. McConechy et al [157] however in a study of the mutation profiles of EEC and EAOC (morphologically similar tumors) have reported differences in PTEN and CTNNB1 profiles.…”

Section: Oncogenes and Tumor Suppressor Genesmentioning

confidence: 99%

“…It is likely that the inflammatory and oxidative-environmental niche during oncogenesis may be reflective of such distinct mutation patterns observed in EEC as compared to EAOCs. While it is plausible that persistent inflammatory niche at ET lesion may cause genetic and epigenetic changes specific to EAOCs [97,158], the question whether OCs with and without concurrent endometriosis develop through common pathogenic pathways remains unsettled due to the fact that a large number of women with EAOCs do not have endometriosis at the time of staging and 1 out of 3 patients with endometrioid or clear-cell OCs show concurrent endometriosis [156]. Also, studies often fail to report whether endometriosis is present with concurrent AE, absence of which may give erroneous construction of such an inference.…”

Section: Oncogenes and Tumor Suppressor Genesmentioning

confidence: 99%

See 1 more Smart Citation

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Ghosh

Anupa

et al. 2019

COGO

View full text Add to dashboard Cite

Endometriosis is an inflammatory disease characterized by the presence of endometrium-like tissue outside the uterus primarily on pelvic organs and tissues. It affects up to 15% of women in the reproductive age group and is often associated with pelvic pain and subfertility. Different theories explain how retrograde menstruation gives rise to endometrial deposits at ectopic sites, and how several other factors are involved in the progression of the disease. Its final diagnosis is established through direct visualization at laparoscopy or surgery followed by histological confirmation. Available epidemiological reports along with histopathological observations and molecular studies shed interesting light on the pathogenetic basis of different variants of the disease like deep infiltrating endometriosis and ovarian endometriosis. Evidence also suggests that endometriosis is a neoplastic condition which serves as a precursor of ovarian and endometrial cancers. In the present review, we have attempted to take a stock of the current epidemiological and molecular knowledge regarding endometriosis associated cancers and develop a model of functional network with interactions among critical genomic factors regulating cellular processes leading to fibrotic reaction. It is being conjectured that cyclic bleeding associated with inflammatory and oxidative stress followed by repeated tissue injury and repair along with recurrent estrogenic stimulation and ovulatory events in the pelvic environment bring about the complex phenotype of atypical endometriosis and associated neoplasm with a trade-off malignant transformation in high risk population. Finally, we have presented an algorithm for pre-emptive monitoring and management of endometriosis-associated cancers.

show abstract

The Endometriotic Tumor Microenvironment in Ovarian Cancer

Cited by 44 publications

References 205 publications

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

Prognostic Characteristics of MACC1 Expression in Epithelial Ovarian Cancer

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Contact Info

Product

Resources

About