Transcript Slayt 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
Endometriosis…to be present
10–15% of women in the reproductive age group..
2–5% of postmenopausal women..
25–30% of infertile women ..
40–70% of women with chronic pelvic pain..
The natural course of endometriosis
starting with ectopic tissue implantation
bleeding in this ectopic tisue
Inflamation
fibrin deposition,
adhesion and scar formation
distortion of peritoneal surfaces
The points of discussion here are to clarify
whether endometriosis should be considered
a precursor lesion of cancer such as, ovarian
uterine and breast and if transformation to
the cancer occurs frequently.
The relationships between endometriosis and cancer
Malignant transformation of endometriosis occurs
generally in 1.7-3.6% of cases.
Ovarian cancer develops in 1–5% of cases with ovarian
endometriosis and in a lower percentage of cases with
extra-ovarian endometriosis.
Endometriosis is present in 10 to 15% of patients with
ovarian cancer.
The course of endometriosis
Jian-Jun Wei and et al Int J Gyncol Patho 2011
Similar factors effect the incidence of ovarian cancer and endometriosis.
Decreased risks
Increased risks
tubal ligation
hysterectomy
oral contraceptives
pregnancy
infertility
early menarche,
Late menopause
Ovarian Cancer and Endometriosis
The relationship between endometriosis and ovarian cancer
RR was 4 in primary infertil patients with endometriosis.
The relationship between endometriosis and ovarian cancer
In this study, dataset consisted of data from 23 144 women.
(7911 with invasive ovarian cancer, 1907 with borderline
ovarian cancer, and 13 326 controls)
* No association was noted between a history of
endometriosis and borderline ovarian cancer.
* History of endometriosis was associated with an
increased risk of invasive epithelial ovarian cancer.
* 2-3 fold increase in the risk of clear-cell, low-grade
serous, and endometrioid invasive ovarian
cancer in patients with endometriosis.
Clinico-pathologic characteristics of ovarian cancer seen in
patients having endometriosis
…….tended
to be younger
earlier stages
to be tumor with lower grade lesions
to be better survival
to be endometrioid and clear cell subtypes
to be diagnosed in
The relation between endometriosis and other cancers
such as breast, cervical and endometrial cancer
The relationship between endometriosis and breast cancer
The relationship between endometriosis and cervical cancer
The relationship between endometriosis and endometrial cancer
There is a relation between endometriosis and ovarian cancer,
so.
endometriosis increases
the risk of ovarian cancer !!!
The weaknesses of the these studies
Most of the cohorts consisted only of patients
hospitalized for endometriosis. This could result in
the inclusion of women with mainly moderate or
severe disease and thereby lead to an overestimation
of the risk of cancer among women with
endometriosis.
Limitation of the studies was the lack of
information on possible confounding factors that
might have influenced the results.
In most of studies, there is no imformation about drug /
hormon use, origin of endometriosis, fertility, parity and
histologic verification of endometriosis.
Causality
between endometriosis and ovarian cancer - I
It is often suggested that a relative risk of at least 2 is
required before the conclusion that a risk estimate can be
considered strong and, in particular, to be free of the influence
of confounders and 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 association between 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.
Causality
between endometriosis and ovarian cancer - II
endometroid or
clear cell ovarian carcinoma
Histological, Genetic and Molecular
Alterations in Endometriosis
Histological Alterations
Atypical endometriosis as a precursor of malignancy
Gynecologic Oncology 77, 298–304 (2000)
Of the 127 patients with ovarian ca, 37(29%) had
histologic evidence of endometriosis. And 70%
of clear cell ca. 43% of endometrioid ca, 7% of
serous ca., and 0% of mucinous ca. had
endometriozis
In 37 cases with endometriosis,
78% showed atypical
endometriosis
The mean Ki-67 indices were as follows: ovarian carcinoma, 23.1;
atypical endometriosis, 9.9; typical endometriosis, 2.7. Atypical
endometriosis shows proliferation activity, suggesting it is a
precancerous status.
Metaplasia
41
12.1 (8.8–16.0)
Hyperplasia
32
9,4 (6.5–13.1)
Atypia
Endometrioid adenoca
20
14
5,9(3.6–9.0)
4.11(2.3–6.9)
Conclusions. Epithelial abnormalities are a common
finding in cystic ovarian endometriosis.
Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical
endometriosis: its close association with malignant epithelial tumours.
Histopathology 1997;30:249–55.
They reported that atypical endometriotic
region were observed in 61% of 54
endometriosis associated ovarian cancers,but
these changes (atypical glandular) were seen in
only 1.7% of 255 endometriosis cases without
cancers.
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 as atypical endometriosis
and 43% cases were typical endometriosis.
With these findings, it is considered that
Atypical endometriosis may represent a transition
from benign endometriosis to carcinoma.
Atypical endometriosis
are considered to be precancerous
lesion.
Genetic alterations in endometriotic tissue I
monoclonality of endometriosis…….. 60-100 % (in 7 studies)
monoclonality of endometriosis…….. 6 % (in 1 study)
Genetic alterations in endometriotic tissue II
loss of heterozygosity (LOH) in endometriosis
commonly involving chromosomes 9p, 11q, and 22q.
Genetic alterations in endometriotic tissue III
P53 mutations
PTEN mutations
K-Ras mutations
in 30% of endometriosis
coexisting with Ovarian CCC
in 20% of endometriotic
cyst, in 20% of EC
and in 8% of CCC
in 10-20% of endometriotic
associated ovarian Ca.
There are conflicting results
Genetic alterations in endometriotic tissue V
ARID1A mutations in endometriosis
ARID1A mutations were seen in
46% of endometriosis associated-ovarian clear-cell ca.
30% of endometriosis associated- ovarian endometrioid ca.
0% of endometriosis associated-high-grade serous ovarian ca.
Wiegand et al. NEMJ 2010
Epigenetic variations in endometriosis
Heme and free iron induced oxidative stress
Inflammation
Steroid hormones
The repetition of hemorrhage in the endometriotic
cysts result in excess accumulation of heme and free
iron in endometriotic lesions. Heme and free iron are
pro-oxidant and can induce oxidative stress and DNA
damage, possibly increasing the risk of some cancer.
Inflammatory cells and cytokines in endometriosis
may promote angiogenesis, cell proliferation,
inhibition of apoptosis, and production of reactive
oxygen species that may induce DNA damage and
mutations. Thus, inflammation may contribute to
tumor growth and progression.
Some studies have demonstrated a local increase
in estradiol concentration in endometriotic lesions.
Estradiol stimulates cyclooxygenase-2 (COX-2).
This can induce DNA damage.
Finaly, endometriosis-associated tumor progression
may be related to many independent factors
Jian-Jun Wei and et al Int J Gyncol Patho 2011
In conclusion,
the exact molecular mechanisms that may lead to
malignant transformation of endometriosis are not
completely understood. The potential etiology
regarding the association between endometriosis
and ovarian cancer seems to be multifactorial.
and
Given the high prevalence of endometriosis
and the high mortality of ovarian cancer, the
potential association has important public
health implications
So, OB&GYNs should be aware of the
apparently increased risk of ovarian cancer
among endometriosis patients, and increased
attention should particularly be paid to
patients with early diagnosis, a longstanding history of disease and/or associated
infertility,
Thank you