Endometrial cancer causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The cause of endometrial cancer has not been identified.
Causes
Genetics
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- In 10–20% of endometrial cancers, mostly Grade 3 (the highest histologic grade), mutations are found in a tumor suppressor gene, commonly TP53 or PTEN.
- In 20% of endometrial hyperplasias and 50% of endometrioid cancers, PTEN suffers a loss-of-function mutation or a null mutation, making it less effective or completely ineffective.[2] Loss of PTEN function leads to up-regulation of the PI3k/Akt/mTOR pathway, which causes cell growth.[3]
- The TP53 pathway can either be suppressed or highly activated in endometrial cancer. When a mutant version of TP53 is overexpressed, the cancer tends to be particularly aggressive. TP53 mutations and chromosome instability are associated with serous carcinomas, which tend to resemble ovarian and Fallopian carcinomas. Serous carcinomas are thought to develop from endometrial intraepithelial carcinoma.[3]
- PTEN and p27 loss of function mutations are associated with a good prognosis, particularly in obese women. The Her2/neu oncogene, which indicates a poor prognosis, is expressed in 20% of endometrioid and serous carcinomas. 'CTNNB1 (beta-catenin; a transcription gene) mutations are found in 14–44% of endometrial cancers and may indicate a good prognosis, but the data is unclear. Beta-catenin mutations are commonly found in endometrial cancers with squamous cells.[3]
- FGFR2 mutations are found in approximately 10% of endometrial cancers, and their prognostic significance is unclear.[2]
- SPOP is another tumor suppressor gene found to be mutated in some cases of endometrial cancer: 9% of clear cell endometrial carcinomas and 8% of serous endometrial carcinomas have mutations in this gene.[4]
- Type I and Type II cancers (explained below) tend to have different mutations involved. ARID1A, which often carries a point mutation in Type I endometrial cancer, is also mutated in 26% of clear cell carcinomas of the endometrium, and 18% of serous carcinomas. Epigenetic silencing and point mutations of several genes are commonly found in Type I endometrial cancer.[5]
- Mutations in tumor suppressor genes are common in Type II endometrial cancer. PIK3CA is commonly mutated in both Type I and Type II cancers. In women with Lynch syndrome-associated endometrial cancer, microsatellite instability is common.[3]
- The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes PTEN, a tumor suppressor; PIK3CA, a kinase; KRAS, a GTPase that functions in signal transduction; and CTNNB1, involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma.[6]
- The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene.[7]
- The p53 cell signaling system is not active in endometrial clear cell carcinoma.[8]
==Microscopic Patho
References
- ↑ International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.
- ↑ 2.0 2.1 Thaker, PH; Sood, AK. "Molecular Oncology in Gynecologic Cancer". In Lentz, GM; Lobo, RA; Gershenson, DM; Katz, VL. Comprehensive Gynecology (6th ed.). Mosby. ISBN 978-0-323-06986-1.
- ↑ 3.0 3.1 3.2 3.3 Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C; et al. (2013). "Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 24 Suppl 6: vi33–8. doi:10.1093/annonc/mdt353. PMID 24078661.
- ↑ Mani, RS (September 2014). "The emerging role of speckle-type POZ protein (SPOP) in cancer development". Drug Discovery Today. 19 (9): 1498–1502. doi:10.1016/j.drudis.2014.07.009. PMID 25058385.
A recent exome-sequencing study revealed that 8% of serious endometrial cancers and 9% of clear cell endometrial cancers have SPOP mutations
- ↑ International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.
- ↑ Colombo, N; Preti, E; Landoni, F; Carinelli, S; Colombo, A; Marini, C; Sessa, C (2011). "Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Annals of Oncology. 22 (Supplement 6): vi35–vi39. doi:10.1093/annonc/mdr374. PMID 21908501.
- ↑ Johnson N, Bryant A, Miles T, Hogberg T, Cornes P (2011). "Adjuvant chemotherapy for endometrial cancer after hysterectomy". Cochrane Database Syst Rev (10): CD003175. doi:10.1002/14651858.CD003175.pub2. PMC 4164379. PMID 21975736.
- ↑ Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR, Ghaem-Maghami S (2011). "Endometrial cancer". BMJ. 343: d3954. doi:10.1136/bmj.d3954. PMID 21734165.