Hypothesis.In women with preeclampsia endovascular remodeling and invasion of the spiral arteries is less prominent which will result in overwhelming placental oxidative stress and pregnancy failure. Abnormal function of trophoblast and stroma cells…
ID
Bron
Verkorte titel
Aandoening
- Maagdarmstelselneoplasmata maligne en niet-gespecificeerd NEG
- Borstneoplasmata maligne en niet-gespecificeerd (incl. tepel)
- Complicaties bij de moeder tijdens de zwangerschap
Synoniemen aandoening
Betreft onderzoek met
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
The stroma-percentage in colon and breast cancer with
- pregnancy outcomes: preeclampsia, intrautiene growth restriction
Secundaire uitkomstmaten
geen
Achtergrond van het onderzoek
Colon and breast cancer are leading causes of cancer-related death in the
Netherlands (10%, 2007 CBS stat line). Survival is directly related to
detection and the type of cancer involved. However, tumor staging
insufficiently discriminates between cancer patients with poor and better
prognosis. Recently Mesker et al, described an independent parameter for
survival using the stroma-percentage within the primary tumor of colon cancer
patients. Patients with high stroma-percentage had a worse survival independent
for either tumor stage, tumor status and lymph node status compared to patients
with a high carcinoma-percentage. The stroma-percentage is available upon
routine HE histological sections. (1,2) For breast cancer this parameter was
validated on a set of 600 patients confirming the results of the former
performed studies. (de Kruijf et al, submitted to JCO)
Pregnancy is also characterized by tumor invasion: adequate placenta invasion
in the uterus is essential in pregnancy outcome.
In normal pregnancy spiral arteries undergo striking remodeling. They change
from typical muscular arteries to flaccid tubes with no muscularis or elastic
lamina with a diameter at least four times greater than that of non-pregnant
vessels. Shortly after the invasion of trophoblasts into the superficial
endometrium, the maternal erythrocytes can be observed within the precursors of
the placental intervillous space. Abnormal placentation is evident in
preeclampsia. Preeclampsia is a pregnancy specific syndrome that is diagnosed
by the new appearance of increased blood pressure and proteinuria. It is a
leading cause of maternal mortality in developed countries and increases
perinatal mortality up to five-fold. Since its etiology is largely unknown,
panoply of pathophysiological abnormalities is described.
Intrauterine growth restriction results also in abnormal placental growth and
angiogenesis with a prevalence of 5%.
Ten percent of the pregnant women will have problems with hypertension during
pregnanacy, of which 3-7% will develop preeclampsia. Inclusion of women with
intrauterine growth restriction will result in at least 5% of the total
population of pregnant women to be involved with abnormal placental growth /
angiogenesis.
Risk factors for abnormal placental growth / angiogenesis / preeclampsia are
advanced maternal age during pregnancy, null parity, multiple gestation,
diabetes, SLE and chronic hypertension. Smoking is a protective factor for
preeclampsia, not for intrauterine growth restriction.
Doel van het onderzoek
Hypothesis.
In women with preeclampsia endovascular remodeling and invasion of the spiral
arteries is less prominent which will result in overwhelming placental
oxidative stress and pregnancy failure. Abnormal function of trophoblast and
stroma cells and their interaction play an important role in abnormal
placentation.
We hypothesize that preeclampsia during pregnancy is an independent, early
clinical genetic marker of invasion for abnormal placental growth, pregnancy
outcome including preeclampsia, intruterine growth restriction, abruptio
placentae as well as cancer with high stroma formation (and thus worse
prognosis).
The expected percentage of women in the population to be investigated would be
5% (12 patients with breast cancer and 17 patients with colon cancer) However,
when a genetic predisposition is the cause of abnormal invasion this percentage
is expected to be much higher in the series to be investigated.
Onderzoeksopzet
Methods.
For women with colon and breast cancer we will determine the stroma-percentage
and gain insight in their pregnancy outcomes. Variables including tumor stage,
tumor status and smoking will be analyzed in a regression analysis.
Abnormal trophoblast invasion is defined in preeclampsia as well as recurrent
abortion, intra-uterine growth restriction and abrutio placentae.
Inschatting van belasting en risico
- We vragen de vrouwen een eenmalige vragenlijst over hun zwangerschap in te
vullen.
- mogelijk is dat emotioneel voor vrouwen echter uit eerder onderzoek bij
vrouwen met een ernstige preeclampsie en/of vroeggeboorte was dit geen probleem
(Gaugler-Senden, paper submitted)
Publiek
Lijnbaans 32
2512 VA den Haag
Nederland
Wetenschappelijk
Lijnbaans 32
2512 VA den Haag
Nederland
Landen waar het onderzoek wordt uitgevoerd
Leeftijd
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Vrouwen met borst kanker en colon kanker behandeld in het LUMC
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
leeftijd < 18 jaar
indien bekend overleden
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