open access
Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer
Affiliations- Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Poland
- Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Poland
- Department of Obstetrics and Gynecology, Pro-Familia Hospital, Rzeszow, Poland
- Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Department of Obstetrics and Gynecology, Fryderyk Chopin University Hospital No 1, Faculty of Medicine, Rzeszow University, Poland
open access
Abstract
Objectives: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS. To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times.
Material and methods: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry.
Results: Patients median age was 54 yrs (range: 29–72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12–23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS.
Conclusions: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents.
Abstract
Objectives: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS. To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times.
Material and methods: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry.
Results: Patients median age was 54 yrs (range: 29–72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12–23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS.
Conclusions: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents.
Keywords
High grade serous ovarian cancer, TEM-7, nestin, disease-free survival, overall survival
About this articleTitle
Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer
Journal
Issue
Article type
Research paper
Pages
135-141
Published online
2018-03-30
Page views
1509
Article views/downloads
1119
DOI
Pubmed
Bibliographic record
Ginekol Pol 2018;89(3):135-141.
Keywords
High grade serous ovarian cancer
TEM-7
nestin
disease-free survival
overall survival
Authors
Artur Czekierdowski
Norbert Stachowicz
Sylwia Czekierdowska
Tomasz Łoziński
Grzegorz Gurynowicz
Tomasz Kluz
References (24)- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7–30.
- Mittempergher L. Genomic Characterization of High-Grade Serous Ovarian Cancer: Dissecting Its Molecular Heterogeneity as a Road Towards Effective Therapeutic Strategies. Curr Oncol Rep. 2016; 18(7): 44.
- McCluggage WG. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology. 2011; 43(5): 420–432.
- Schmid BC, Oehler MK. New perspectives in ovarian cancer treatment. Maturitas. 2014; 77(2): 128–136.
- Karakaya BK, Başer E, Bildacı B, et al. Alternative tumor markers in the diagnosis of ovarian cancer. Ginekol Pol. 2016; 87(8): 565–769.
- Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005; 307(5706): 58–62.
- Markowska A, Sajdak S, Markowska J, et al. Angiogenesis and cancer stem cells: New perspectives on therapy of ovarian cancer. Eur J Med Chem. 2017; 142: 87–94.
- Croix B, Rago C, Velculescu V, et al. Genes Expressed in Human Tumor Endothelium. Science. 2000; 289(5482): 1197–1202.
- He QZ, Luo XZ, Zhou Q, et al. Expression of nestin in ovarian serous cancer and its clinicopathologic significance. Eur Rev Med Pharmacol Sci. 2013; 17(21): 2896–2901.
- Neradil J, Veselska R. Nestin as a marker of cancer stem cells. Cancer Sci. 2015; 106(7): 803–811.
- Osman WM, Shash LS, Ahmed NS. Emerging Role of Nestin as an Angiogenesis and Cancer Stem Cell Marker in Epithelial Ovarian Cancer: Immunohistochemical Study. Appl Immunohistochem Mol Morphol. 2017; 25(8): 571–580.
- Czekierdowska S, Stachowicz N, Chróściel M, et al. Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B. Ginekol Pol. 2017; 88(3): 120–128.
- Svachova H, Kryukov F, Kryukova E, et al. Nestin expression throughout multistep pathogenesis of multiple myeloma. Br J Haematol. 2014; 164(5): 701–709.
- Bagley RG, Rouleau C, Weber W, et al. Tumor endothelial marker 7 (TEM-7): a novel target for antiangiogenic therapy. Microvasc Res. 2011; 82(3): 253–262.
- Pietrzyk Ł. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates. Dis Markers. 2016; 2016: 4912405.
- Zhang ZZ, Hua R, Zhang JF, et al. TEM7 (PLXDC1), a key prognostic predictor for resectable gastric cancer, promotes cancer cell migration and invasion. Am J Cancer Res. 2015; 5(2): 772–781.
- Nanda A, Buckhaults P, Seaman S, et al. Identification of a binding partner for the endothelial cell surface proteins TEM7 and TEM7R. Cancer Res. 2004; 64(23): 8507–8511.
- Fuchs B, Mahlum E, Halder C, et al. High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma. Gene. 2007; 399(2): 137–143.
- Kupryjanczyk J, Kraszewska E, Ziolkowska-Seta I, et al. TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study. BMC Cancer. 2008; 8.
- Qin Q, Sun Y, Fei M, et al. Expression of putative stem marker nestin and CD133 in advanced serous ovarian cancer. Neoplasma. 2012; 59(3): 310–315.
- Sal V, Kahramanoglu I, Bese T, et al. Is serum level of nestin useful in detecting epithelial ovarian cancer? J Obstet Gynaecol Res. 2017; 43(2): 371–377.
- Zhang Y, Zeng S, Ma J, et al. Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance. J Exp Clin Cancer Res. 2016; 35(1): 111.
- Wang XQ, Sheibani N, Watson JC. Modulation of tumor endothelial cell marker 7 expression during endothelial cell capillary morphogenesis. Microvasc Res. 2005; 70(3): 189–197.
- Mehran R, Nilsson M, Khajavi M, et al. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy. Cancer Res. 2014; 74(10): 2731–2741.
