Identification of pre-malignancies found in the endometrium as possible precursor lesions of the serous papillary ovarian carcinoma in BRCA1 and/or BRCA2 mutation bearing women.

Ovarian carcinoma is, after endometrium carcinoma, the most frequent cancer in
women with a life-time risk of 1-2% and, more importantly, has a high death
rate among gynaecologic cancers in the western world. 75% of the patients with
ovarian cancer are diagnosed with a high FIGO stadium (III or IV), resulting in
high mortality rates. In addition, women with a deleterious mutation in the
BRCA1 and/or BRCA2 gene have an increased risk of ovarian cancer, ranging from
10 to 60 percent. Mutations in either of these genes increase susceptibility to
cancers of the ovary, fallopian tube, breast and peritoneum.
As holds true for other cancer types, early identification of (pre-) malignant
lesions of ovarian cancer could positively influence the treatment and
prognosis of patients. However, the last 35 years never a precursor lesion for
ovarian cancer has been identified.
Currently, a completely new theory about ovarian cancer is emerging, with the
site of origin in the endometrium. Possibly, pre-malignant lesions arise within
the endometrium from where tumour cells detach and travel via the physiological
flow to the fallopian tube, ovaries and peritoneum. This new theory is based on
the following observations:
1) The pathologist cannot morphologically differentiate between serous
papillary carcinoma of different origins (endometrium, fallopian tube and
ovaries). In addition, histological, immuno-histological and genetically, there
are many similarities among tumours of this type, possibly suggesting the same
precursor cell. 2) The last decennia, new data reveal a pre-malignant lesion
within the endometrium (EmGD), possibly giving rise to serous papillary
carcinomas when the lesion progresses. Currently, this pre-malignancy is only
associated with the serous papillary carcinoma of the uterus. 3) Interestingly,
hysterectomy and/or tubal ligation do decrease the cancer risk by 43-46%,
suggesting that the origin of ovarian cancer could very well be located within
the uterus.
Concluding, conformation of this new hypothesis would change the current view
on the aetiology of ovarian cancer, which possibly has dramatic implications
for diagnosing, treatment and prognosis of patients with this type of cancer.

Identification of pre-malignancies found in the endometrium, obtained by
dilatation & curettage, as possible precursor lesions of the serous papillary
ovarian carcinoma.

The patient who undergoes a planned prophylactic bilateral
salpingo-oophorectomy, will also recieve a dilatation & curettage of the
uterus. This material is investigated by the pathologist for possible presence
of (pre-) malignancies.

The additional burden for the patient is minimal, since the additional duration
of the anaesthesia is only 10 minutes. Although there is a chance of uterus
perforation (0,12-0,14%, Aydeniz et al., 2002), in this study this additional
risk will be even lower by the fact that every included patient will receive an
ultrasound to reveal the orientation of their uterus. Furthermore, the
additional burden will be minimal since only experienced gynaecologists will
perform this intervention and the group of included patients consists of young,
healthy women with a low a-priori chance on complications. Afterwards, patients
could have some complaints about pain or vaginal bleeding for a maximum of 3
days.