Sugar-Sweetened Beverage Intake and the Risk of Type I and Type II Endometrial Cancer among Postmenopausal Women

One of the strategies used by tumors to evade immunosurveillance is the accumulation of extracellular adenosine, which has immunosupressive and tumor promoting effects. The study of the mechanisms leading to adenosine formation at the tumor interstitium are therefore of great interest in oncology. The dominant pathway generating extracellular adenosine in tumors is the dephosphorylation of ATP by ecto-nucleotidases. Two of these enzymes acting sequentially, CD39 and CD73, efficiently hydrolyze extracellular ATP to adenosine. They have been found to play a crucial role in a variety of tumors, but there were no data concerning endometrial cancer, the most frequent of the invasive tumors of the female genital tract. The aim of the present work is to study the expression of CD39 and CD73 in human endometrial cancer. We have analyzed protein and gene expression, as well as enzyme activity, in type I endometrioid adenocarcinomas and type II serous adenocarcinomas and their nonpathological endometrial counterparts. High levels of both enzymes were found in tumor samples, with significantly increased expression of CD39 in type II serous tumors, which also coincided with the higher tumor grade. Our results reinforce the involvement of the adenosinergic system in cancer, emphasizing the relevance of ecto-nucleotidases as emerging therapeutic targets in oncology.

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Differential Impact of Systemic Lymphadenectomy Upon the Survival of Patients with Type I vs Type II Endometrial Cancer: A Retrospective Observational Cohort Study

Cancer Management and Research ◽

10.2147/cmar.s280780 ◽

2020 ◽

Vol Volume 12 ◽

pp. 12269-12276

Author(s):

Jie Xu ◽

Can Chen ◽

Jing Xiong ◽

Hua Linghu

Keyword(s):

Endometrial Cancer ◽

Cohort Study ◽

Observational Cohort Study ◽

Type I ◽

Type Ii ◽

Differential Impact ◽

Observational Cohort ◽

Retrospective Observational Cohort Study

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Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late

International Journal of Molecular Sciences ◽

10.3390/ijms19082380 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2380 ◽

Cited By ~ 13

Author(s):

Michiel Remmerie ◽

Veerle Janssens

Keyword(s):

Clinical Trials ◽

Endometrial Cancer ◽

Targeted Therapies ◽

Kinase Inhibitors ◽

Therapeutic Potential ◽

Treatment Options ◽

Genetic Alterations ◽

Mitogen Activated Protein Kinase ◽

Type I ◽

Type Ii

Type II endometrial carcinomas (ECs) are responsible for most endometrial cancer-related deaths due to their aggressive nature, late stage detection and high tolerance for standard therapies. However, there are no targeted therapies for type II ECs, and they are still treated the same way as the clinically indolent and easily treatable type I ECs. Therefore, type II ECs are in need of new treatment options. More recently, molecular analysis of endometrial cancer revealed phosphorylation-dependent oncogenic signalling in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways to be most frequently altered in type II ECs. Consequently, clinical trials tested pharmacologic kinase inhibitors targeting these pathways, although mostly with rather disappointing results. In this review, we highlight the most common genetic alterations in type II ECs. Additionally, we reason why most clinical trials for ECs using targeted kinase inhibitors had unsatisfying results and what should be changed in future clinical trial setups. Furthermore, we argue that, besides kinases, phosphatases should no longer be ignored in clinical trials, particularly in type II ECs, where the tumour suppressive phosphatase protein phosphatase type 2A (PP2A) is frequently mutated. Lastly, we discuss the therapeutic potential of targeting PP2A for (re)activation, possibly in combination with pharmacologic kinase inhibitors.

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Nuclear Type II Estradiol Binding Sites and Type I Estrogen Receptors in Human Endometrial Cancer: A 5-Year Follow-Up Study

Gynecologic Oncology ◽

10.1006/gyno.1993.1015 ◽

1993 ◽

Vol 48 (1) ◽

pp. 94-103 ◽

Cited By ~ 4

Author(s):

J.L. Környei ◽

T. Csermely ◽

G. Keller ◽

M. Véertes

Keyword(s):

Endometrial Cancer ◽

Estrogen Receptors ◽

Binding Sites ◽

Type I ◽

Type Ii ◽

Follow Up Study

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Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer

British Journal of Cancer ◽

10.1038/bjc.2013.540 ◽

2013 ◽

Vol 109 (7) ◽

pp. 1908-1913 ◽

Cited By ~ 21

Author(s):

S Uccella ◽

A Mariani ◽

A H Wang ◽

R A Vierkant ◽

W A Cliby ◽

...

Keyword(s):

Endometrial Cancer ◽

Type I ◽

Type Ii

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Associated characteristics and impact on recurrence and survival of free-floating tumor fragments in the lumen of fallopian tubes in Type I and Type II endometrial cancer

Gynecologic Oncology Reports ◽

10.1016/j.gore.2018.01.003 ◽

2018 ◽

Vol 23 ◽

pp. 28-33 ◽

Cited By ~ 2

Author(s):

Benjamin B. Albright ◽

Jonathan D. Black ◽

Rachel Passarelli ◽

Stefan Gysler ◽

Margaret Whicker ◽

...

Keyword(s):

Endometrial Cancer ◽

Type I ◽

Type Ii ◽

Fallopian Tubes

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Lynch Syndrome Identification in Endometrial Cancer Patients: Should Universal Screening be Used for all Histologies?

Current Women s Health Reviews ◽

10.2174/1573404817666210302153551 ◽

2021 ◽

Vol 17 ◽

Author(s):

Jessica E. Parker ◽

Caitlin Mauer ◽

Wenxin Zheng ◽

David S. Miller ◽

Jayanthi S. Lea

Keyword(s):

Endometrial Cancer ◽

Genetic Testing ◽

Family History ◽

Lynch Syndrome ◽

Cancer Patients ◽

Universal Screening ◽

Type I ◽

Type Ii ◽

Screening Approach ◽

Endometrial Cancers

Background: There is an increased proportion of non-endometrioid histologies in Lynch syndrome-associated compared to sporadic endometrial cancer, however screening recommendations do not differ between type I and type II cancers. Objective: Our objective was to examine the frequency of Lynch syndrome identified in type I and type II endometrial cancers and their associated characteristics. Methods: We reviewed patients with type I and type II endometrial cancer who were screened for Lynch Syndrome or referred for genetic testing according to an age and family-history based screening protocol. All patients were seen and treated at large academic institution affiliated with a county safety-net hospital. Clinical, pathologic, immunohistochemistry, and germline genetic testing results were obtained as well as choice of genetic screening approach, personal and family history, and compliance with testing. Results: 234 women with type I and 29 patients with type II endometrial cancer were identified. Lynch syndrome was diagnosed in a total of eight (3.4%) type I endometrial cancer patients, all identified after age-based tumor screening. In the type II endometrial cancer group, three (10.3%) patients had Lynch syndrome. One was referred for testing after abnormal immunohistochemistry screening under age 60. The other two were >60 years old and identified after abnormal immunohistochemistry screening performed by physician request. Conclusion: Age based screening may not diagnose Lynch Syndrome in women with type II endometrial cancers. Our findings underscore the need for a universal screening approach in patients with type II endometrial cancers, even in a low resource population.

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