Authors: Annika J Bock Helene Tuft Stavnes Janne Kærn Aasmund Berner Anne Cathrine Staff Ben Davidson
Publish Date: 2011/02/26
Volume: 32, Issue: 3, Pages: 589-596
Abstract
Endoglin CD105 a cell surface coreceptor for transforming growth factorβ is expressed in proliferating endothelial cells as well as in cancer cells We studied endoglin expression and its clinical relevance in effusions primary tumors and solid metastatic lesions from women with advancedstage ovarian serous carcinoma Endoglin expression was analyzed by immunohistochemistry in effusions n = 211 174 peritoneal 37 pleural Cellular endoglin staining was analyzed for association with the concentration of soluble endoglin previously determined by ELISA in 95 corresponding effusions and analyzed for correlation with clinicopathologic parameters including survival Endoglin expression was additionally studied in 34 patientmatched primary tumors and solid metastases Carcinoma and mesothelial cells expressed endoglin in 95/211 45 and 133/211 63 effusions respectively Carcinoma cell endoglin expression was more frequent in effusions from patients aged ≤60 years p = 0048 and in post compared to prechemotherapy effusions p = 0014 whereas mesothelial cell endoglin expression was higher in prechemotherapy effusions p = 0021 No association was found between cellular endoglin expression and its soluble effusion concentration Endoglin was expressed in 17/34 50 primary tumors and 19/34 56 metastases with significantly higher percentage of immunostained cells in solid metastases compared to effusions p = 0036 Endoglin expression did not correlate with survival Tumor cell endoglin expression is higher in post vs prechemotherapy effusions whereas the opposite is seen in mesothelial cells Together with its upregulation in solid metastases this suggests that the expression and biological role of endoglin may differ between cell populations and change along tumor progression in ovarian carcinomaOvarian carcinoma OC makes up 90 of all ovarian cancers 1 and is the leading cause of gynecological cancer death in Western countries 2 Two thirds of OC patients present with metastases at diagnosis The peritoneum omentum pelvis and abdominal viscera are common sites of seeding and more than any other neoplasm OC is associated with development of ascites 3 The pleural cavity constitutes the most frequent location of extraabdominal disease 4 There is an ongoing search for highly sensitive and specific biomarkers to improve early diagnosis and thereby reduce morbidity and mortality of OC New prognostic and predictive markers are needed to better assess patient outcome and guide individual therapiesEndoglin CD105 is a 180kDa homodimeric glycoprotein composed of two 95 kDa disulfidelinked subunits It has a transmembrane structure and functions as a component of the transforming growth factorβ receptor complex Endoglin is highly expressed on proliferating endothelial cells and is critical for angiogenesis Endoglinstimulated tumor angiogenesis is probably regulated via hypoxia which is among the few known inducers of endoglin production 5 6A soluble form of endoglin sEng is found in the circulation under normal and pathologic conditions Breast and colorectal cancer patients exhibit higher sEng serum concentrations than healthy individuals with the highest concentrations found in patients with metastatic disease 5 sEng is increased in sera of pregnant women and is markedly elevated in preeclamptic patients The serum sEng concentration increases prior to the onset of preeclampsia and correlates with disease severity 7 8Endoglin immunoreactivity in endothelial cells has been used to determine intratumoral microvessel density MVD of solid neoplasms High endoglindetermined MVD correlates with metastatic disease and low survival rates in a range of human malignancies including breast gastrointestinal prostate cervical and head/neck cancer 9 10 11 12 13 14 15 Taskiran et al demonstrated endoglin expression evaluated as MVD to be an independent predictor of poor overall survival OS in OC 16 However Rubatt et al postulated that high endoglinassessed MVD predicts increased risk of OC progression but not increased risk of diseaserelated death 17Malignant cells express endoglin in the cytoplasm although staining is less frequent than in endothelial cells 5 Henriksen et al found endoglin expression in OC cells of primary tumors but without significant difference from the expression seen in normal ovarian epithelium High OC cell endoglin staining correlated with short OS 18 We have recently found that high tumor cell endoglin expression in breast cancer effusions independently predicts poor diseasefree survival and OS 19Similarly to the situation in breast cancer effusions endoglin expression in OC effusions could be a marker of disease outcome This theory is supported by the prognostic value of endoglin found in OC primary tumors 18 and by the presence of high sEng concentrations in plasma and effusions from OC patients 20 In the present study we analyzed endoglin expression in OC effusions and its association with clinicopathologic parameters including survival in a large cohort of patients with serous carcinoma Endoglin expression in effusions was compared to that in primary tumors and solid metastatic lesions from the same patients Effusion cells were considered a source of sEng and cellular endoglin expression was therefore compared to the sEng concentration in corresponding effusions
Keywords: