Zusammenfassung
Die Krebsinzidenz auf dem Boden einer bestehenden Endometriose wird auf rund 0,7 -
1 % geschätzt. Eine ovarielle Endometriose scheint mit 2,5 % noch häufiger zu entarten.
Retrospektive Studien verzeichneten ein erhöhtes Risiko bei Frauen mit Endometriose
vor allem für Schilddrüsenkarzinome (standardisierte Inzidenzrate SIR 4,65), Ovarialkarzinome
(SIR 1,43 - 4,2) und Non-Hodgkin-Lymphome (SIR 1,24 - 3,2). Die Adenomyosis uteri
dagegen scheint kein erhöhtes Risiko für Malignome zu haben. Die Assoziation zwischen
Endometriose und Ovarialkarzinomen wurde durch klinische Untersuchungen belegt. Nach
achtjähriger Krankheitsdauer findet bei 0,7 % der Patientinnen eine maligne Umwandlung
der Endometriose statt. Andererseits wurde Endometriose zu 40 - 70 % gleichzeitig
mit klarzelligen Adenokarzinomen und zu 21 - 43 % gleichzeitig mit endometrioiden
Adenokarzinomen identifiziert. Seltener war Endometriose mit serösen (3 - 9 %) oder
muzinösen Adenokarzinomen (0 - 3 %) assoziiert. Da sich Endometriose-assoziierte Ovarialkarzinome
(EAOC) von anderen Ovarialkarzinomen unterscheiden, wurde dieser Begriff im Sinne
einer neuen Entität eingeführt. Patientinnen mit einem Endometriose-assoziierten Ovarialkarzinom
haben im Vergleich zu Patientinnen mit anderen Ovarialkarzinomen ein niedrigeres Tumorstadium,
eine unterschiedliche Verteilung der histologischen Unterarten (am häufigsten endometrioide
und klarzellige Karzinome) und eine signifikant bessere Überlebensrate (80 - 100 %).
Außerdem erkranken Frauen mit Endometriose früher in ihrem Leben an einem Ovarialkarzinom
(45,9 ± 8,9 Jahre) als Frauen ohne Endometriose (54,9 ± 16,2 Jahre). Auch eine atypische
Endometriose ist häufig mit epithelialen Ovarialkarzinomen assoziiert. Sie tritt bei
rund 60 - 80 % der Endometriose-assoziierten Ovarialkarzinome auf, wobei 25 % direkt
in ein Ovarialkarzinom übergehen. Die Inflammation scheint ein wichtiger pathogenetischer
Faktor sowohl beim Ovarialkarzinom als auch bei der Endometriose zu sein. Mutagene
Eigenschaften der Entzündungsreaktion können durch Zellzerstörung, oxidativen Stress
und erhöhte Zytokin- und Prostaglandinspiegel verursacht sein. Neben Endometriose
und Inflammation zählen zu den weiteren Risikofaktoren eines Ovarialkarzinoms Infertilität,
Asbest, Talk und Hyperöstrogenismus bei Adipositas. Protektive Faktoren sind Tubensterilisation,
Hysterektomie, Geburten und orale Kontrazeptiva. Bei einer malignen Transformation
der Endometriose entfallen 80 % auf das Ovar und 20 % auf extragonadale Manifestationen.
Letztere waren im Allgemeinen mit Östrogensubstitutionstherapien verknüpft. Der Verlust
von genetischem Material wurde auf mehreren Genloci im Endometriosegewebe entdeckt
und ist potenziell mit der Inaktivierung von Tumorsuppressorgenen assoziiert. Die
kausale Verbindung zwischen Endometriose und Ovarialkarzinom scheint sowohl durch
diese Assoziationen als auch durch die zugrunde liegenden molekularen Mechanismen
definiert zu sein.
Abstract
The risk of cancer arising from pre-existing endometriosis is estimated to be around
0.7 - 1 %. With an incidence of 2.5 %, ovarian endometriosis is suggested to transform
even more frequently into ovarian cancer. Retrospective studies have shown an increased
risk for some types of malignancy for endometriosis patients, especially for thyroid
tumours (standardised incidence ratio SIR 4.65), ovarian cancer (SIR 1.43 - 4.2) and
Non-Hodgkin's lymphoma (SIR 1.24 - 3.2). Adenomyosis uteri seems not to be related
to an increased cancer risk. The association between endometriosis and ovarian cancer
was proved by clinical studies. Malignant transformation of endometriosis is reported
in 0.7 % of all endometriosis patients after eight years. On the other hand, endometriosis
was identified in 40 - 70 % of clear cell carcinomas and in 21 - 43 % of endometrioid
carcinomas. Endometriosis was rarely associated with serous (3 - 9 %) or mucinous
carcinomas (0 - 3 %). Since endometriosis-associated ovarian cancer (EAOC) differs
from other types of ovarian cancers, this concept was introduced as a new entity.
Women with endometriosis-associated ovarian cancer most likely represent a different
class of patients compared to traditional ovarian cancer patients. The patients with
EAOC usually have a lower stage disease, show a completely different distribution
of histological subtypes (significant overrepresentation of endometrioid and clear
cell carcinomas), have predominantly lower grade lesions, and they have a statistically
significant better overall survival (80 - 100 %). Furthermore, among patients with
malignant tumours, those with endometriosis were statistically significant younger
(45.9 ± 8.9 years) compared to those without endometriosis (54.9 ± 16.2 years). An
atypical endometriosis is also frequently associated with epithelial ovarian cancer.
It appears in about 60 - 80 % of endometriosis-associated ovarian cancers and 25 %
showed a direct transition into ovarian cancer. Inflammation seems to be a pathophysiological
contributor for ovarian cancer as well as for endometriosis. Mutagenic qualities of
the inflammatory reaction could be caused by cell damage, oxidative stress and elevation
of cytokines and prostaglandins. In addition to endometriosis and inflammation, further
risk factors for ovarian cancer are infertility, asbestos, talcum and hyperoestrogenism.
Protective factors are tubal ligation, hysterectomy, births and oral contraceptives.
Malignant transformation of endometriosis occurs in the ovary in 80 % and in extragonadal
sites in 20 %. The latter were generally associated with oestrogen substitution therapies.
The loss of genetic material was discovered on several gene loci in endometriosis
tissue and is potentially associated with inactivation of tumour suppressor genes.
The causal link between endometriosis and ovarian cancer remains to be defined both
in terms of entity of association and of underlying molecular mechanisms.
Schlüsselwörter
Endometriose - Ovarialkarzinom - maligne Transformation - Inzidenzraten
Key words
Endometriosis - ovarian cancer - malignant transformation - incidence ratios
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PD Dr. Daniela Hornung
Universitätsfrauenklinik
Ratzeburger Allee 160
23538 Lübeck
Email: D.Hornung@gmx.de
