title: High immunohistochemical expression of TGF-β1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density.
abstract: Endoglin, a coreceptor for transforming growth factor β1 (TGF-β1) in vascular endothelial cells, is highly upregulated in tumor vessels and therefore is a specific biomarker for angiogenesis. Some studies have suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy and radiotherapy. In this study, we attempted to analyze the immunohistochemical expression of endoglin and TGF-β1 from 80 patients with different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer before they received concurrent chemoradiation and to investigate their prognostic significance. The median follow-up period was 86 months (range, 2-144 months). Endoglin staining was assessed by microvessel density (MVD), whereas TGF-β1 expression was semiquantified as negative, weakly, or strongly staining. A receiver operating characteristic curve was established for endoglin MVD in predicting survival; the optimal cutoff value was 11.125. With a Cox regression analysis, we found that an advanced FIGO stage (hazard ratio 4.66; 95% confidence interval 2.10-10.32, P<0.001) and endoglin MVD more than 11.125 (hazard ratio 12.21; 95% confidence interval 3.62-41.16, P=<0.001) were independent factors to predict survival. Interestingly, a strong TGF-β1 expression was significantly associated with poor survival only when the endoglin MVD value was higher than 10. Our study shows that evaluation of endoglin MVD by immunochemistry can be used as an independent prognostic marker for cervical cancer patients receiving concurrent chemoradiation. TGF-β1 also had an impact on survival only when endoglin MVD was enriched, suggesting its involvement in tumor progression in the later stage of angiogenesis.
authors: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Hao
authors: H
authors: Lin
authors: Chao-Cheng
authors: CC
authors: Huang
authors: Yu-Che
authors: YC
authors: Ou
authors: Eng-Yen
authors: EY
authors: Huang
authors: Chan-Chao
authors: CC
authors: Changchien
authors: Chih-Wen
authors: CW
authors: Tseng
authors: Hung-Chun
authors: HC
authors: Fu
authors: Chen-Hsuan
authors: CH
authors: Wu
authors: Chia-Jung
authors: CJ
authors: Li
authors: Yen-Ying
authors: YY
authors: Ma
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D000071063:Endoglin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis*; D053773:Transforming Growth Factor beta1 / Q000032:analysis* / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1