Endometriose und Malignomrisiko

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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