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| __NOTOC__ | | __NOTOC__ |
| {{Endometrial cancer}} | | {{Endometrial cancer}} |
| {{CMG}} | | {{CMG}}{{AE}}{{MD}} |
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| ==Overview== | | ==Overview== |
| The cause of endometrial cancer has not been identified.
| | Causes of endometrial cancer include genetic mutations of the ''[[KRAS]]'' gene, ''[[TP53]]'' gene, ''[[P16 (gene)|TP16]]'' gene, and/or ''[[PTEN]]'' gene. Other genetic mutations have also been described. |
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| ==Causes== | | ==Causes== |
| ==Genetics==
| | Endometrial cancer arises following multiple genetic mutations. The following genes are involved in the development of endometrial cancer: |
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| |+Mutations found in Type I and Type II endometrial cancers<ref>International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.</ref> | | |+Mutations found in Type I and Type II endometrial cancers<ref>International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.</ref> |
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| * In 10–20% of endometrial cancers, mostly Grade 3 (the highest [[Grading (tumors)|histologic grade]]), [[mutation]]s are found in a [[tumor suppressor]] gene, commonly ''[[TP53]]'' or ''[[PTEN (gene)|PTEN]]''.
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| * In 20% of [[endometrial hyperplasia]]s and 50% of endometrioid cancers, ''[[PTEN]]'' suffers a loss-of-function mutation or a null mutation, making it less effective or completely ineffective.<ref name=ComprehensiveGyn26/> Loss of PTEN function leads to up-regulation of the PI3k/Akt/mTOR pathway, which causes cell growth.<ref name="pmid24078661">{{cite journal| author=Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C et al.| title=Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal=Ann Oncol | year= 2013 | volume= 24 Suppl 6 | issue= | pages= vi33-8 | pmid=24078661 | doi=10.1093/annonc/mdt353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24078661 }} </ref>
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| * 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.<ref name="pmid24078661">{{cite journal| author=Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C et al.| title=Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal=Ann Oncol | year= 2013 | volume= 24 Suppl 6 | issue= | pages= vi33-8 | pmid=24078661 | doi=10.1093/annonc/mdt353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24078661 }} </ref>
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| * ''[[PTEN]]'' and ''[[p27 (gene)|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 (genetics)|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 cell]]s.<ref name="pmid24078661">{{cite journal| author=Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C et al.| title=Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up}}. | journal=Ann Oncol | year= 2013 | volume= 24 Suppl 6 | issue= | pages= vi33-8 | pmid=24078661 | doi=10.1093/annonc/mdt353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24078661 }</ref>
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| * ''[[FGFR2]]'' mutations are found in approximately 10% of endometrial cancers, and their prognostic significance is unclear.<ref name=ComprehensiveGyn26>{{cite book |last1=Thaker |first1=PH |last2=Sood |first2=AK |chapter=Molecular Oncology in Gynecologic Cancer |editor-last1=Lentz |editor-first1=GM |editor-last2=Lobo |editor-first2=RA |editor-last3=Gershenson |editor-first3=DM |editor-last4=Katz |editor-first4=VL|displayeditors=4 |title=Comprehensive Gynecology |edition=6th |isbn=978-0-323-06986-1 |publisher=[[Mosby (publisher)|Mosby]]}}</ref>
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| * ''[[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.<ref>{{cite journal|last1=Mani|first1=RS|title=The emerging role of speckle-type POZ protein (SPOP) in cancer development.|journal=Drug Discovery Today|date=September 2014|volume=19|issue=9|pages=1498–1502|doi=10.1016/j.drudis.2014.07.009|pmid=25058385|quote="A recent exome-sequencing study revealed that 8% of serious endometrial cancers and 9% of clear cell endometrial cancers have SPOP mutations"}}</ref>
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| * 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. [[Gene silencing|Epigenetic silencing]] and [[point mutations]] of several genes are commonly found in Type I endometrial cancer.<ref>International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.</ref>
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| * 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.<ref name="pmid24078661">{{cite journal| author=Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C et al.| title=Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal=Ann Oncol | year= 2013 | volume= 24 Suppl 6 | issue= | pages= vi33-8 | pmid=24078661 | doi=10.1093/annonc/mdt353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24078661 }} </ref>
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| * 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.<ref name=annonc>{{cite journal |last1=Colombo |first1=N |last2=Preti |first2=E |last3=Landoni |first3=F |last4=Carinelli |first4=S |last5=Colombo |first5=A |last6=Marini |first6=C |last7=Sessa |first7=C |year=2011 |title=Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up |journal=Annals of Oncology |volume=22 |issue=Supplement 6 |pages=vi35–vi39 |doi=10.1093/annonc/mdr374 |pmid=21908501}}</ref>
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| * The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in ''[[TP53]]'', an important tumor suppressor gene.<ref name="pmid21975736">{{cite journal| author=Johnson N, Bryant A, Miles T, Hogberg T, Cornes P| title=Adjuvant chemotherapy for endometrial cancer after hysterectomy. | journal=Cochrane Database Syst Rev | year= 2011 | volume= | issue= 10 | pages= CD003175 | pmid=21975736 | doi=10.1002/14651858.CD003175.pub2 | pmc=PMC4164379 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21975736 }} </ref>
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| * The p53 cell signaling system is not active in endometrial clear cell carcinoma.<ref name="pmid21734165">{{cite journal| author=Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR, Ghaem-Maghami S| title=Endometrial cancer. | journal=BMJ | year= 2011 | volume= 343 | issue= | pages= d3954 | pmid=21734165 | doi=10.1136/bmj.d3954 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21734165 }} </ref>
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| ==Microscopic Patho
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
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| | [[Category:Up-To-Date]] |
| | [[Category:Oncology]] |
| | [[Category:Medicine]] |
| | [[Category:Gynecology]] |
| | [[Category:Surgery]] |