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Is endometriosis a prenoplastic condition ?

Is endometriosis a prenoplastic condition ?. Prof. Dr. Fuat Demirkıran I.U Cerrahpaşa School of Medicine. Department o f OB&GYN Division Of Gynocol Oncol Asian Con. on Endometriosis Nowember Istanbul. Endometriosis … to be present 10–15% of women in the reproductive age group ..

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Is endometriosis a prenoplastic condition ?

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  1. Is endometriosis a prenoplastic condition ? Prof. Dr. Fuat Demirkıran I.U Cerrahpaşa School of Medicine. Department of OB&GYN Division Of Gynocol Oncol Asian Con. on Endometriosis Nowember Istanbul

  2. Endometriosis…to be present 10–15% of women in the reproductive agegroup.. 2–5% of postmenopausal women.. 25–30% ofinfertile women .. 40–70% of women with chronic pelvicpain..

  3. The natural course of endometriosis startingwithectopic tissue implantation bleeding in thisectopictisue Inflamation fibrin deposition, adhesionandscarformation distortion ofperitoneal surfaces

  4. The points of discussion here are to clarify whether endometriosis should be considered a precursorlesion of cancersuch as, ovarianuterineandbreastand if transformationtothecancer occurs frequently.

  5. Therelationshipsbetweenendometriosisandcancer Malignanttransformation of endometriosisoccursgenerallyin 1.7-3.6% of cases. Ovarian cancer develops in 1–5% ofcases with ovarian endometriosis and in a lower percentageof cases with extra-ovarian endometriosis. Endometriosis ispresent in 10 to 15% of patients with ovarian cancer.

  6. Thecourse of endometriosis Jian-JunWeiand et al Int J GyncolPatho 2011

  7. Similar factors effect the incidence ofovariancancerandendometriosis. Decreasedrisks tuballigation hysterectomy oral contraceptives pregnancy Increased risks infertility early menarche, Latemenopause OvarianCancerandEndometriosis

  8. Therelationshipbetweenendometriosisandovariancancer RR was 4 in primaryinfertilpatientswithendometriosis.

  9. Therelationshipbetweenendometriosisandovariancancer

  10. Inthisstudy, dataset consisted of data from 23 144 women.(7911 with invasive ovarian cancer, 1907 with borderlineovarian cancer, and 13 326 controls) * No association was noted between a history ofendometriosis and borderline ovarian cancer. * History of endometriosis was associated with an increasedrisk of invasive epithelial ovarian cancer. * 2-3 fold increase inthe risk of clear-cell, low-grade serous,andendometrioidinvasiveovarian cancer in patientswithendometriosis.

  11. Clinico-pathologiccharacteristics of ovariancancerseen in patientshavingendometriosis …….tended to be younger to be diagnosed in earlier stages to betumorwithlower grade lesions to be bettersurvival to be endometrioid and clearcellsubtypes

  12. Therelationbetweenendometriosisandothercancers such as breast, cervicalandendometrialcancer

  13. Therelationshipbetweenendometriosisandbreastcancer

  14. Therelationshipbetweenendometriosisandcervicalcancer

  15. Therelationshipbetweenendometriosisandendometrialcancer

  16. There is a relationbetweenendometriosis and ovariancancer, so. endometriosisincreasesthe risk of ovariancancer !!!

  17. Theweaknesses of thethesestudies Most of the cohorts consisted only ofpatients hospitalized for endometriosis. This could result in theinclusion of women with mainly moderate or severe disease andthereby lead to an overestimation of the risk of cancer among womenwithendometriosis. Limitation of the studies was the lack ofinformation on possible confounding factors that might haveinfluencedtheresults. Inmost of studies, there is no imformationaboutdrug / hormon use, origin of endometriosis, fertility, parityand histologicverification of endometriosis.

  18. Causality between endometriosis and ovarian cancer - I It is often suggested that a relative risk of at least 2 is requiredbefore the conclusion that a risk estimate can be consideredstrong and, in particular, to be free of the influence of confoundersand other sources of bias and selectivity. Relative risks of less than 2.0 may also be consistent with causality. Overall, the reported strength of association between endometriosis and ovarian cancer ranged between 1.3 and 4. Despite the weak association, majority of studies documented statistically significant associationbetween endometriosis and ovarian cancer. Some studies found that the cancer risk markedly increased in women having a long-standing history of the disease. This finding suports the causal association.

  19. Causality between endometriosis and ovarian cancer - II endometroid or clear cell ovarian carcinoma

  20. Histological, Genetic and MolecularAlterations in Endometriosis

  21. HistologicalAlterations Atypicalendometriosis as a precursor of malignancy

  22. Gynecologic Oncology 77, 298–304 (2000) Of the 127 patients with ovarian ca, 37(29%) had histologic evidence of endometriosis. And 70% of clear cellca. 43% of endometrioidca,7% of serousca., and0% of mucinousca. had endometriozis In 37 cases with endometriosis, 78% showed atypical endometriosis ThemeanKi-67 indices were as follows: ovarian carcinoma, 23.1; atypicalendometriosis, 9.9; typicalendometriosis, 2.7. Atypical endometriosis shows proliferation activity, suggesting it is a precancerous status.

  23. Metaplasia 41 12.1 (8.8–16.0) Hyperplasia 32 9,4 (6.5–13.1) Atypia 20 5,9(3.6–9.0) Endometrioidadenoca 14 4.11(2.3–6.9) Conclusions. Epithelial abnormalities are a common finding incysticovarianendometriosis.

  24. Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology 1997;30:249–55. Theyreportedthatatypicalendometrioticregion were observed in 61% of 54 endometriosisassociatedovarian cancers,but thesechanges (atypicalglandular) were seen in only 1.7% of255 endometriosis cases without cancers.

  25. Retrospective analysis of 160 malignant and 23 borderline ovarian tumours during the period 1995–2001. 7.7% of the ovarian ca tumours contained endometriosis. The incidence of ovarian endometriosis in borderline tumours was 13% compared to in ovarian cancer 6.9%. Endometriosis observed in 22% of the endometrioid, 9% of clear cell ca and 10.8% of the mixed adeno adenoca 57% of cases were classified asatypical endometriosis and43%cases were typical endometriosis.

  26. Withthesefindings, it is consideredthat Atypical endometriosis may represent a transition frombenignendometriosistocarcinoma. Atypicalendometriosis are considered to be precancerouslesion.

  27. Genetic alterations in endometriotic tissue I monoclonality of endometriosis…….. 60-100 % (in 7 studies) monoclonality of endometriosis…….. 6 % (in 1 study)

  28. Genetic alterations in endometriotic tissue II loss of heterozygosity (LOH) inendometriosis commonlyinvolving chromosomes9p, 11q, and 22q.

  29. Genetic alterations in endometriotic tissue III in 30% of endometriosis coexistingwithOvarian CCC P53 mutations PTEN mutations K-Rasmutations in 20% of endometriotic cyst, in 20% of EC and in 8% of CCC in 10-20% of endometriotic associatedovarianCa. There are conflicting results

  30. Genetic alterations in endometriotic tissue V ARID1A mutations in endometriosis ARID1A mutations were seen in 46% of endometriosisassociated-ovarian clear-cell ca. 30% of endometriosisassociated- ovarianendometrioid ca. 0% ofendometriosisassociated-high-grade serous ovarianca. Wiegand et al. NEMJ 2010

  31. Epigeneticvariations in endometriosis Heme and free iron induced oxidative stress Inflammation Steroidhormones

  32. The repetition of hemorrhage in the endometrioticcystsresult in excess accumulationof heme and free iron in endometriotic lesions. Heme and free iron are pro-oxidant and can induce oxidativestress and DNA damage, possibly increasing the risk of some cancer. Inflammatorycellsandcytokines in endometriosismay promote angiogenesis, cell proliferation, inhibition of apoptosis, and production of reactive oxygen speciesthat mayinduce DNA damage and mutations. Thus, inflammationmay contribute to tumor growth and progression. Some studies have demonstrated alocalincrease in estradiolconcentration in endometrioticlesions. Estradiol stimulates cyclooxygenase-2 (COX-2). Thiscan induce DNA damage.

  33. Finaly, endometriosis-associated tumor progression may be related to many independent factors Jian-JunWeiand et al Int J GyncolPatho 2011

  34. In conclusion, the exactmolecularmechanisms that may lead tomalignanttransformation of endometriosis are not completely understood.The potential etiology regarding the association betweenendometriosis and ovarian cancer seems to be multifactorial. and Giventhehighprevalence of endometriosis and the high mortality of ovarian cancer, the potential association has important public health implications

  35. So, OB&GYNs should beaware of the apparently increased risk of ovarian cancer amongendometriosis patients, and increased attention should particularly bepaid to patients with early diagnosis, a long- standing history ofdiseaseand/orassociatedinfertility,

  36. Thankyou

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