Intended for healthcare professionals

Clinical Review

Endometrial cancer

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d3954 (Published 06 July 2011) Cite this as: BMJ 2011;343:d3954

Re: Endometrial cancer

Introduction:
Worldwide in 2008, 288,000 women were diagnosed with uterine cancer while the mortality rate from endometrial cancer was 1.7 to 2.4 per 100,000 women (1). Uterine cancer is the fourth most common gynecologic malignancy in Peninsular Malaysia (2). Most current update describes that in the United States 44,717 women were diagnosed with uterine cancer in 2010 and among them 8,402 women died from this deadly disease(3).We read the insightful clinical review article "Endometrial Cancer" and applauded the in-depth discussion on investigative procedures for symptomatic cases.

However,we are concerned that till date there is no screening test available for large scale screening and monitoring for endometrial cancer in asymptomatic average risk population. Therefore, there is an urgent need of a robust, non invasive, cost effective tool for large scale screening, early detection and prognostic monitoring of endometrial carcinoma.

Background:
Modern histopathological diagnostics for endometrial carcinoma includes microscopic cellular and tissue diagnostics, for demonstrating the presence of cancer and precancerous conditions.

Histopathological diagnostics is the gold standard test for endometrial carcinoma in every single step from screening to diagnosis and also in choosing a treatment plan and in monitoring the cancer patient for cure or relapse (4).

MOLECULAR TUMOR MARKERS or BIOMARKERS:

The term tumor marker is used in international literature to mean an organ-specific material of which an elevated amount is present in body fluids of cancer patients, whereas in similar body fluids it would appear in only low concentrations if at all in a healthy person or a person who did not have a tumor. Even though such biomarkers are generally seemed to be not specific, they have become an important tool in the early recognition that a tumor is present or have recurred.

In Hungary, tumor markers are not tested to the extent that international expectations would warrant (5).

Despite incredible advancement in cutting age molecular technologies seen in 21st century, endometrial cancer is perhaps the least studied and understood cancer affecting women. Unfortunately at present no screening tests or tests for early detection and monitoring for recurrence are available for endometrial cancer in women who belong to average risk group but have no symptoms.

microRNA EXPRESSION PROFILING IN ENDOMETRIAL CARCINOMA:

In the past few years, substantial progress has been made in the arenas of clinical trials and translational research. An area of recent interest is the relative expression patterns of microRNAs (miRNAs) in cancer and how these molecules contribute to oncogenesis.

MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) of approximately 22 bp that induce RNA interference with a complementary messenger RNA (mRNA) and act in silencing of mRNA. miRNAs are strongly associated with cancer development and those involved in carcinogenesis are classified into oncogenic miRNAs and tumor suppressor miRNAs (tumor suppressor miRs). Specific miRNAs are expressed in various tissues and changes in regulation of gene expression are thought to cause carcinogenesis. Thus, tissue-specific miRNAs may be biomarkers for cancer diagnosis and prognosis.(4) Earlier Fenshi Zhan et al., reported that MicroRNA-10b (miR-10b) has been positively involved in the migration of a number of tumor cells lineages (5).

In the recent past, we appreciated the clinical application of the MicroRNA signature classifier (MSC) Lung Cancer assay which significantly reduced the false positive rate and the potential side effects associated with repeated LDCT scans or other unnecessary invasive diagnostic follow-ups(6).

In endometrial cancer, miRNAs are associated with regulation of gene expression, epigenetic dysfunction and carcinogenesis. Thus, miRNAs are likely to have key roles in diagnosis, prognostic prediction. Laura Romero-Pérez et al., reported that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis (7).An exploratory study to find a single microRNA or a group of microRNAs which are specific to endometrial cancer tissue may solve this emerging problem.

ADAMs (A Disintegrin And Metalloproteinases) EXPRESSION PROFILING IN ENDOMETRIAL CARCINOMA:

ADAMs is a family of multifunctional proteases ( a disintegrin and metalloproteinases) that direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties and also promotes cell migration and invasion in several tumor cell lines (8-13).

The metalloprotease family of enzymes is integral to the process of tumor progression, from angiogenesis and cell migration to remodeling of the tumor microenvironment, invasion, and metastasis. In the recent past Sushan E Pories et al., reported that urinary matrix metalloproteinases (MMPs) and ADAM 12 could be detected in the urine of breast cancer patients and these urinary metalloproteinases could be used as biomarkers to predict breast cancer risk status (14). An analysis on ADAMs expression profiling may help us to find a co-biomarker for endometrial carcinoma.

References:
1. World cancer research fund international. Cancer facts and figures: Endometrial cancer rates. http://www.wcrf.org/cancer_statistics/cancer_facts/endometrial_cancer_ra... (Accessed on January 30, 2013).
2. http://www.makna.org.my/PDF/MalaysiaCancerStatistics.pdf
3. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2010 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2013. http://www.cdc.gov/uscs.
4. http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial...
5. http://www.iccp-portal.org/sites/default/files/plans/Hungary_National_Ca...
Control_Programme_English.pdf
6. MicroRNAs in endometrial cancer. (2013) Banno K1, Yanokura M, Kisu I, Yamagami W, Susumu N, Aoki D. Int J Clin Oncol. 2013 Apr;18(2):186-92. doi: 10.1007/s10147-013-0526-9. Epub 2013 Feb 5.
7. Laura Romero-Pérez, M Ángeles López-García et al.,ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma:(2013)Modern Pathology 26, 1514-1524 (November 2013) | doi:10.1038/modpathol.2013.93
8. Tanu Pramanik, Lecturer; Hj Abdul Halim Hj Mansar, Professor ; Narazah Mohd. Yusoff, Professor ; Jogenananda Pramanik, Professor : (January 14, 2014 ) Simple, cost effective, minimally invasive or non-invasive molecular screening test for lung cancer- A need of the hour! http://annals.org/article.aspx?articleid=1809422
9. Fenxi Zhang, Suhua Jing, Tongming Ren, Juntang Lin (2013) microRNA-10b promotes the migration of mouse bone marrow-derived mesenchymal stem cells and downregulates the expression of E-cadherin. Molecular Medicine Reports (Impact Factor: 1.17). 08/2013; DOI:10.3892/mmr.2013.1615
10. Lin Juntang, 1 Wang Congrui,2 Jogenananda Pramanik, et al.,(2004) Study on construction of cDNA libraries from rat normal liver and regeneration liver with smart technique; Indian J Clin Biochem. 2004 July; 19(2): 177–180. doi: 10.1007/BF02894281,PMCID: PMC3454212
11.Lin Juntang, Jogenananda Pramanik, Wang Congrui, Zhang Huiyong, Feng Huigen, Yang Baosheng, Li Yuchang, Xu Cunshuan (2004) Study on construction of cDNA library of the treated changliver cell and quality analysis. Indian Journal of Clinical Biochemistry 07/2004; 19(2):181-3.
12. Congrui Wang, Huiyong Zhang, Huigen Feng, Baosheng Yang, Jogenananda Pramanik, Zhikun Guo, Juntang Lin (2010)Molecular characterization and functional analysis of a protease-related protein in Chang-liver cells. BMB reports 05/2010; 43(5):375-81
13. Xin Yan, Juntang Lin, Venkata Ajay Narendra Talabattula, Carolin Mußmann, Fan Yang, Andreas Wree, Arndt Rolfs, Jiankai Luo : ADAM10 Negatively Regulates Neuronal Differentiation during Spinal Cord Development. PLoS ONE (Impact Factor: 3.73). 01/2014; 9(1):e84617. DOI:10.1371/journal.pone.0084617
14. Susan E. Pories, David Zurakowski,Roopali Roy et al., Urinary Metalloproteinases: Noninvasive Biomarkers for Breast Cancer Risk Assessment (2008) Cancer Epidemiol Biomarkers Prev May 2008 17; 1034: doi: 10.1158/1055-9965.EPI-07-0365.

Competing interests: Prof.Dr.J.Pramanik is also the Dean of International students affair in Caribbean Medical University School of Medicine,Curacao,Netherlands Antillies and Dr.Lin Juntang is also employed as Vice Dean in Xinxiang Medical University,Xinxiang City, China.

26 February 2014
Prof. Dr. Jogenananda Pramanik MBBS.MD
Professor & Director of Research & Post Graduate Studies
Dr. Lin Juntang PhD Jena University, Jena, Germany
Allianze University College of Medical Sciences
Waziria Medical Square,Jalan bertam-2, Kepala batas-13200,Pulau Pinang,Malaysia