Skip to main content
Top
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Review

Prognostic value of microvessel density in cervical cancer

Authors: Xiaoli Hu, Hailing Liu, Miaomiao Ye, Xueqiong Zhu

Published in: Cancer Cell International | Issue 1/2018

Login to get access

Abstract

Background

Several epidemiological researches have indicated that microvessel density (MVD), reflecting angiogenesis, was a negatively prognostic factor of cervical cancer. However, the results were inconsistent. Therefore, we performed a meta-analysis to evaluate the association between microvessel density and the survival probability of patients with cervical cancer.

Method

There was a comprehensive search of the PubMed, EMBASE and Cochrane databases up to August 31, 2017. Based on a fixed-effects or random-effects model, the hazard ratio (HR) and 95% confidence intervals (CIs) were calculated from researches on overall survival (OS) and disease-free survival (DFS).

Result

Totally, we included 13 observational researches, involving 1097 patients with cervical cancer. The results showed that high level of microvessel density was negatively correlated with OS (HR = 1.79, 95% CIs 1.31–2.44, I2 = 60.7%, P = 0.003) and DFS (HR = 1.47, 95% CIs 1.13–1.80, I2 = 0%, P = 0.423) of cervical cancer patients. In subgroup analysis, high counts of MVD were significantly associated with a poor survival (including OS and DFS) of the patients detected by anti-factor VIII antibodies or in European origin.

Conclusion

The present meta-analysis indicated that survival with high level of MVD was significant poorer than with low MVD in cervical cancer patient. Standardization of MVD assessment is needed.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef
2.
go back to reference Kress CM, Sharling L, Owen-Smith AA, Desalegn D, Blumberg HM, Goedken J. Knowledge, attitudes, and practices regarding cervical cancer and screening among Ethiopian health care workers. Int J Womens Health. 2015;7:765–72.PubMedPubMedCentral Kress CM, Sharling L, Owen-Smith AA, Desalegn D, Blumberg HM, Goedken J. Knowledge, attitudes, and practices regarding cervical cancer and screening among Ethiopian health care workers. Int J Womens Health. 2015;7:765–72.PubMedPubMedCentral
3.
go back to reference Intaraphet S, Kasatpibal N, Siriaunkgul S, Sogaard M, Patumanond J, Khunamornpong S, Chandacham A, Suprasert P. Prognostic impact of histology in patients with cervical squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma. Asian Pac J Cancer Prev. 2013;14(9):5355–60.CrossRef Intaraphet S, Kasatpibal N, Siriaunkgul S, Sogaard M, Patumanond J, Khunamornpong S, Chandacham A, Suprasert P. Prognostic impact of histology in patients with cervical squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma. Asian Pac J Cancer Prev. 2013;14(9):5355–60.CrossRef
4.
go back to reference Horn LC, Bilek K, Fischer U, Einenkel J, Hentschel B. A cut-off value of 2 cm in tumor size is of prognostic value in surgically treated FIGO stage IB cervical cancer. Gynecol Oncol. 2014;134(1):42–6.CrossRef Horn LC, Bilek K, Fischer U, Einenkel J, Hentschel B. A cut-off value of 2 cm in tumor size is of prognostic value in surgically treated FIGO stage IB cervical cancer. Gynecol Oncol. 2014;134(1):42–6.CrossRef
5.
go back to reference Leek RD. The prognostic role of angiogenesis in breast cancer. Anticancer Res. 2001;21(6B):4325–31.PubMed Leek RD. The prognostic role of angiogenesis in breast cancer. Anticancer Res. 2001;21(6B):4325–31.PubMed
6.
go back to reference Jilaveanu LB, Puligandla M, Weiss SA, Wang XV, Zito C, Flaherty KT, Boeke M, Neumeister V, Camp RL, Adeniran A, et al. Tumor microvessel density as a prognostic marker in high-risk renal cell carcinoma patients treated on ECOG-ACRIN E2805. Clin Cancer Res. 2018;24(1):217–23.CrossRef Jilaveanu LB, Puligandla M, Weiss SA, Wang XV, Zito C, Flaherty KT, Boeke M, Neumeister V, Camp RL, Adeniran A, et al. Tumor microvessel density as a prognostic marker in high-risk renal cell carcinoma patients treated on ECOG-ACRIN E2805. Clin Cancer Res. 2018;24(1):217–23.CrossRef
7.
go back to reference Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324(1):1–8.CrossRef Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324(1):1–8.CrossRef
8.
go back to reference Cao F, Hu YW, Li P, Liu Y, Wang K, Ma L, Li PF, Ni CR, Ding HZ. Lymphangiogenic and angiogenic microvessel density in chinese patients with gastric carcinoma: correlation with clinicopathologic parameters and prognosis. Asian Pac J Cancer Prev. 2013;14(8):4549–52.CrossRef Cao F, Hu YW, Li P, Liu Y, Wang K, Ma L, Li PF, Ni CR, Ding HZ. Lymphangiogenic and angiogenic microvessel density in chinese patients with gastric carcinoma: correlation with clinicopathologic parameters and prognosis. Asian Pac J Cancer Prev. 2013;14(8):4549–52.CrossRef
9.
go back to reference Cantu De Leon D, Lopez-Graniel C, Frias Mendivil M, Chanona Vilchis G, Gomez C, De La Garza Salazar J. Significance of microvascular density (MVD) in cervical cancer recurrence. Int J Gynecol Cancer. 2003;13(6):856–62.CrossRef Cantu De Leon D, Lopez-Graniel C, Frias Mendivil M, Chanona Vilchis G, Gomez C, De La Garza Salazar J. Significance of microvascular density (MVD) in cervical cancer recurrence. Int J Gynecol Cancer. 2003;13(6):856–62.CrossRef
10.
go back to reference Cooper RA, Wilks DP, Logue JP, Davidson SE, Hunter RD, Roberts SA, West CM. High tumor angiogenesis is associated with poorer survival in carcinoma of the cervix treated with radiotherapy. Clin Cancer Res. 1998;4(11):2795–800.PubMed Cooper RA, Wilks DP, Logue JP, Davidson SE, Hunter RD, Roberts SA, West CM. High tumor angiogenesis is associated with poorer survival in carcinoma of the cervix treated with radiotherapy. Clin Cancer Res. 1998;4(11):2795–800.PubMed
11.
go back to reference Lee JS, Choi YD, Lee JH, Nam JH, Choi C, Lee MC, Park CS, Kim HS, Min KW. Expression of PTEN in the progression of cervical neoplasia and its relation to tumor behavior and angiogenesis in invasive squamous cell carcinoma. J Surg Oncol. 2006;93(3):233–40.CrossRef Lee JS, Choi YD, Lee JH, Nam JH, Choi C, Lee MC, Park CS, Kim HS, Min KW. Expression of PTEN in the progression of cervical neoplasia and its relation to tumor behavior and angiogenesis in invasive squamous cell carcinoma. J Surg Oncol. 2006;93(3):233–40.CrossRef
12.
go back to reference Petsuksiri J, Chuangsuwanich T, Pattaranutaporn P, Kanngurn S. Angiogenesis in stage IIIB squamous cell carcinoma of uterine cervix: reproducibility of measurement and preliminary outcome as a prognostic factor. J Med Assoc Thai. 2004;87(7):794–9.PubMed Petsuksiri J, Chuangsuwanich T, Pattaranutaporn P, Kanngurn S. Angiogenesis in stage IIIB squamous cell carcinoma of uterine cervix: reproducibility of measurement and preliminary outcome as a prognostic factor. J Med Assoc Thai. 2004;87(7):794–9.PubMed
13.
go back to reference Dai C, Wang M, Lu J, Dai Z, Lin S, Yang P, Tian T, Liu X, Min W, Dai Z. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis. OncoTargets Ther. 2017;10:3625–34.CrossRef Dai C, Wang M, Lu J, Dai Z, Lin S, Yang P, Tian T, Liu X, Min W, Dai Z. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis. OncoTargets Ther. 2017;10:3625–34.CrossRef
14.
go back to reference Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.CrossRef Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.CrossRef
15.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRef
16.
go back to reference Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323(7304):101–5.CrossRef Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323(7304):101–5.CrossRef
17.
go back to reference Dellas A, Moch H, Schultheiss E, Feichter G, Almendral A, Gudat F, Torhorst J. Association of tumor induced vascularization with clinicopathological parameters in cervical neoplasm. Int J Oncol. 1997;11(1):105–9.PubMed Dellas A, Moch H, Schultheiss E, Feichter G, Almendral A, Gudat F, Torhorst J. Association of tumor induced vascularization with clinicopathological parameters in cervical neoplasm. Int J Oncol. 1997;11(1):105–9.PubMed
18.
go back to reference Hockel S, Schlenger K, Vaupel P, Hockel M. Association between host tissue vascularity and the prognostically relevant tumor vascularity in human cervical cancer. Int J Oncol. 2001;19(4):827–32.PubMed Hockel S, Schlenger K, Vaupel P, Hockel M. Association between host tissue vascularity and the prognostically relevant tumor vascularity in human cervical cancer. Int J Oncol. 2001;19(4):827–32.PubMed
19.
go back to reference Kaku T, Hirakawa T, Kamura T, Amada S, Kinukawa N, Kobayashi H, Sakai K, Ariyoshi K, Sonoda K, Nakano H. Angiogenesis in adenocarcinoma of the uterine cervix. Cancer. 1998;83(7):1384–90.CrossRef Kaku T, Hirakawa T, Kamura T, Amada S, Kinukawa N, Kobayashi H, Sakai K, Ariyoshi K, Sonoda K, Nakano H. Angiogenesis in adenocarcinoma of the uterine cervix. Cancer. 1998;83(7):1384–90.CrossRef
20.
go back to reference Moriyama S, Kotera K, Khan KN, Sato F, So Y, Fujishita A, Matsuda K, Nakajima H, Ishimaru TEA. Prognostic significance of tumor volume and microvessel density in squamous cell carcinoma of uterine cervix. Acta Med Nagasakiensia. 2009;53(4):77–84. Moriyama S, Kotera K, Khan KN, Sato F, So Y, Fujishita A, Matsuda K, Nakajima H, Ishimaru TEA. Prognostic significance of tumor volume and microvessel density in squamous cell carcinoma of uterine cervix. Acta Med Nagasakiensia. 2009;53(4):77–84.
21.
go back to reference Randall LM, Monk BJ, Darcy KM, Tian C, Burger RA, Liao SY, Peters WA, Stock RJ, Fruehauf JP. Markers of angiogenesis in high-risk, early-stage cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2009;112(3):583–9.CrossRef Randall LM, Monk BJ, Darcy KM, Tian C, Burger RA, Liao SY, Peters WA, Stock RJ, Fruehauf JP. Markers of angiogenesis in high-risk, early-stage cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2009;112(3):583–9.CrossRef
22.
go back to reference Schlenger K, Hockel M, Mitze M, Schaffer U, Weikel W, Knapstein PG, Lambert A. Tumor vascularity—a novel prognostic factor in advanced cervical carcinoma. Gynecol Oncol. 1995;59(1):57–66.CrossRef Schlenger K, Hockel M, Mitze M, Schaffer U, Weikel W, Knapstein PG, Lambert A. Tumor vascularity—a novel prognostic factor in advanced cervical carcinoma. Gynecol Oncol. 1995;59(1):57–66.CrossRef
23.
go back to reference Zijlmans HJ, Fleuren GJ, Hazelbag S, Sier CF, Dreef EJ, Kenter GG, Gorter A. Expression of endoglin (CD105) in cervical cancer. Br J Cancer. 2009;100(10):1617–26.CrossRef Zijlmans HJ, Fleuren GJ, Hazelbag S, Sier CF, Dreef EJ, Kenter GG, Gorter A. Expression of endoglin (CD105) in cervical cancer. Br J Cancer. 2009;100(10):1617–26.CrossRef
24.
go back to reference van der Veldt AA, Hooft L, van Diest PJ, Berkhof J, Buist MR, Comans EF, Hoekstra OS, Molthoff CF. Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence. Eur J Nucl Med Mol Imaging. 2006;33(12):1408–16.CrossRef van der Veldt AA, Hooft L, van Diest PJ, Berkhof J, Buist MR, Comans EF, Hoekstra OS, Molthoff CF. Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence. Eur J Nucl Med Mol Imaging. 2006;33(12):1408–16.CrossRef
25.
go back to reference Tjalma W, Van Marck E, Weyler J, Dirix L, Van Daele A, Goovaerts G, Albertyn G, van Dam P. Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer. Br J Cancer. 1998;78(2):170–4.CrossRef Tjalma W, Van Marck E, Weyler J, Dirix L, Van Daele A, Goovaerts G, Albertyn G, van Dam P. Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer. Br J Cancer. 1998;78(2):170–4.CrossRef
26.
go back to reference Obermair A, Wanner C, Bilgi S, Speiser P, Kaider A, Reinthaller A, Leodolter S, Gitsch G. Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival. Am J Obstet Gynecol. 1998;178(2):314–9.CrossRef Obermair A, Wanner C, Bilgi S, Speiser P, Kaider A, Reinthaller A, Leodolter S, Gitsch G. Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival. Am J Obstet Gynecol. 1998;178(2):314–9.CrossRef
27.
go back to reference Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res. 2004;64(9):2941–55.CrossRef Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res. 2004;64(9):2941–55.CrossRef
28.
go back to reference Yu M, Liu L, Liang C, Li P, Ma X, Zhang Q, Wei Y. Intratumoral vessel density as prognostic factors in head and neck squamous cell carcinoma: a meta-analysis of literature. Head Neck. 2014;36(4):596–602.CrossRef Yu M, Liu L, Liang C, Li P, Ma X, Zhang Q, Wei Y. Intratumoral vessel density as prognostic factors in head and neck squamous cell carcinoma: a meta-analysis of literature. Head Neck. 2014;36(4):596–602.CrossRef
29.
go back to reference Nowak A, Grzegrzolka J, Paprocka M, Piotrowska A, Rys J, Matkowski R, Dziegiel P. Nestin-positive microvessel density is an independent prognostic factor in breast cancer. Int J Oncol. 2017;51(2):668–76.CrossRef Nowak A, Grzegrzolka J, Paprocka M, Piotrowska A, Rys J, Matkowski R, Dziegiel P. Nestin-positive microvessel density is an independent prognostic factor in breast cancer. Int J Oncol. 2017;51(2):668–76.CrossRef
30.
go back to reference Barbu I, Craitoiu S, Simionescu CE, Dragnei AM, Margaritescu C. CD105 microvessels density, VEGF, EGFR-1 and c-erbB-2 and their prognostic correlation in different subtypes of cervical adenocarcinoma. Rom J Morphol Embryol. 2013;54(3):519–30.PubMed Barbu I, Craitoiu S, Simionescu CE, Dragnei AM, Margaritescu C. CD105 microvessels density, VEGF, EGFR-1 and c-erbB-2 and their prognostic correlation in different subtypes of cervical adenocarcinoma. Rom J Morphol Embryol. 2013;54(3):519–30.PubMed
31.
go back to reference Vieira SC, Silva BB, Pinto GA, Vassallo J, Moraes NG, Santana JO, Santos LG, Carvasan GA, Zeferino LC. CD34 as a marker for evaluating angiogenesis in cervical cancer. Pathol Res Pract. 2005;201(4):313–8.CrossRef Vieira SC, Silva BB, Pinto GA, Vassallo J, Moraes NG, Santana JO, Santos LG, Carvasan GA, Zeferino LC. CD34 as a marker for evaluating angiogenesis in cervical cancer. Pathol Res Pract. 2005;201(4):313–8.CrossRef
32.
go back to reference Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R, Iki M. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56(11):2671–6.PubMed Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R, Iki M. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56(11):2671–6.PubMed
Metadata
Title
Prognostic value of microvessel density in cervical cancer
Authors
Xiaoli Hu
Hailing Liu
Miaomiao Ye
Xueqiong Zhu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0647-3

Other articles of this Issue 1/2018

Cancer Cell International 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine