Skip to main content
Top
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Primary Tumor Vascularity, HIF-1α and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact

Authors: Hari Prasad Dhakal, Jahn M Nesland, Mette Førsund, Claes G Trope, Ruth Holm

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled.

Methods

Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1α and VEGF expression and clinicopathological factors and clinical outcome were evaluated.

Results

High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1α (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1α expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001).

Conclusions

A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1α expression in vulvar carcinomas was a statistically independent prognostic factor.
Appendix
Available only for authorised users
Literature
1.
go back to reference Giles GG, Kneale BL: Vulvar cancer: the Cinderella of gynaecological oncology. Aust N Z J Obstet Gynaecol. 1995, 35: 71-75. 10.1111/j.1479-828X.1995.tb01835.x.CrossRefPubMed Giles GG, Kneale BL: Vulvar cancer: the Cinderella of gynaecological oncology. Aust N Z J Obstet Gynaecol. 1995, 35: 71-75. 10.1111/j.1479-828X.1995.tb01835.x.CrossRefPubMed
2.
go back to reference Coulter J, Gleeson N: Local and regional recurrence of vulval cancer: management dilemmas. Best Pract Res Clin Obstet Gynaecol. 2003, 17: 663-681. 10.1016/S1521-6934(03)00050-6.CrossRefPubMed Coulter J, Gleeson N: Local and regional recurrence of vulval cancer: management dilemmas. Best Pract Res Clin Obstet Gynaecol. 2003, 17: 663-681. 10.1016/S1521-6934(03)00050-6.CrossRefPubMed
3.
go back to reference Jones RW, Baranyai J, Stables S: Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol. 1997, 90: 448-452. 10.1016/S0029-7844(97)00298-6.CrossRefPubMed Jones RW, Baranyai J, Stables S: Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol. 1997, 90: 448-452. 10.1016/S0029-7844(97)00298-6.CrossRefPubMed
4.
go back to reference Messing MJ, Gallup DG: Carcinoma of the vulva in young women. Obstet Gynecol. 1995, 86: 51-54. 10.1016/0029-7844(95)00101-V.CrossRefPubMed Messing MJ, Gallup DG: Carcinoma of the vulva in young women. Obstet Gynecol. 1995, 86: 51-54. 10.1016/0029-7844(95)00101-V.CrossRefPubMed
5.
go back to reference Beller U, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Maisonneuve P, Pecorelli S, Odicino F, Heintz AP: Carcinoma of the vulva. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006, 95 (1): S7-27.CrossRefPubMed Beller U, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Maisonneuve P, Pecorelli S, Odicino F, Heintz AP: Carcinoma of the vulva. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006, 95 (1): S7-27.CrossRefPubMed
6.
go back to reference Nayha VV, Stenback FG: Increased angiogenesis is associated with poor prognosis of squamous cell carcinoma of the vulva. Acta Obstet Gynecol Scand. 2007, 86: 1392-1397. 10.1080/00016340701674303.CrossRefPubMed Nayha VV, Stenback FG: Increased angiogenesis is associated with poor prognosis of squamous cell carcinoma of the vulva. Acta Obstet Gynecol Scand. 2007, 86: 1392-1397. 10.1080/00016340701674303.CrossRefPubMed
7.
go back to reference Wang Z, Trope CG, Florenes VA, Suo Z, Nesland JM, Holm R: Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes. BMC Cancer. 2010, 10: 233-10.1186/1471-2407-10-233.CrossRefPubMedPubMedCentral Wang Z, Trope CG, Florenes VA, Suo Z, Nesland JM, Holm R: Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes. BMC Cancer. 2010, 10: 233-10.1186/1471-2407-10-233.CrossRefPubMedPubMedCentral
8.
go back to reference Tyring SK: Vulvar squamous cell carcinoma: guidelines for early diagnosis and treatment. Am J Obstet Gynecol. 2003, 189: S17-S23. 10.1067/S0002-9378(03)00792-0.CrossRefPubMed Tyring SK: Vulvar squamous cell carcinoma: guidelines for early diagnosis and treatment. Am J Obstet Gynecol. 2003, 189: S17-S23. 10.1067/S0002-9378(03)00792-0.CrossRefPubMed
9.
go back to reference Stehman FB, Look KY: Carcinoma of the vulva. Obstet Gynecol. 2006, 107: 719-733. 10.1097/01.AOG.0000202404.55215.72.CrossRefPubMed Stehman FB, Look KY: Carcinoma of the vulva. Obstet Gynecol. 2006, 107: 719-733. 10.1097/01.AOG.0000202404.55215.72.CrossRefPubMed
10.
go back to reference Folkman J: What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst. 1990, 82: 4-6. 10.1093/jnci/82.1.4.CrossRefPubMed Folkman J: What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst. 1990, 82: 4-6. 10.1093/jnci/82.1.4.CrossRefPubMed
11.
go back to reference Folkman J: Angiogenesis: an organizing principle for drug discovery?. Nat Rev Drug Discov. 2007, 6: 273-286. 10.1038/nrd2115.CrossRefPubMed Folkman J: Angiogenesis: an organizing principle for drug discovery?. Nat Rev Drug Discov. 2007, 6: 273-286. 10.1038/nrd2115.CrossRefPubMed
12.
go back to reference Vermeulen PB, Libura M, Libura J, O'Neill PJ, Van DP, Van ME, Van Oosterom AT, Dirix LY: Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Breast Cancer Res Treat. 1997, 42: 165-172. 10.1023/A:1005737524541.CrossRefPubMed Vermeulen PB, Libura M, Libura J, O'Neill PJ, Van DP, Van ME, Van Oosterom AT, Dirix LY: Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Breast Cancer Res Treat. 1997, 42: 165-172. 10.1023/A:1005737524541.CrossRefPubMed
13.
go back to reference Offersen BV, Borre M, Overgaard J: Quantification of angiogenesis as a prognostic marker in human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density. Eur J Cancer. 2003, 39: 881-890. 10.1016/S0959-8049(02)00663-9.CrossRefPubMed Offersen BV, Borre M, Overgaard J: Quantification of angiogenesis as a prognostic marker in human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density. Eur J Cancer. 2003, 39: 881-890. 10.1016/S0959-8049(02)00663-9.CrossRefPubMed
14.
go back to reference Dhakal HP, Naume B, Synnestvedt M, Borgen E, Kaaresen R, Schlichting E, Wiedswang G, Bassarova A, Giercksky KE, Nesland JM: Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination. Clin Cancer Res. 2008, 14: 2341-2350. 10.1158/1078-0432.CCR-07-4214.CrossRefPubMed Dhakal HP, Naume B, Synnestvedt M, Borgen E, Kaaresen R, Schlichting E, Wiedswang G, Bassarova A, Giercksky KE, Nesland JM: Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination. Clin Cancer Res. 2008, 14: 2341-2350. 10.1158/1078-0432.CCR-07-4214.CrossRefPubMed
15.
go back to reference Hantschmann P, Jeschke U, Friese K: TGF-alpha, c-erbB-2 expression and neoangiogenesis in vulvar squamous cell carcinoma. Anticancer Res. 2005, 25: 1731-1737.PubMed Hantschmann P, Jeschke U, Friese K: TGF-alpha, c-erbB-2 expression and neoangiogenesis in vulvar squamous cell carcinoma. Anticancer Res. 2005, 25: 1731-1737.PubMed
16.
go back to reference Abulafia O, Triest WE, Sherer DM: Angiogenesis in malignancies of the female genital tract. Gynecol Oncol. 1999, 72: 220-231. 10.1006/gyno.1998.5152.CrossRefPubMed Abulafia O, Triest WE, Sherer DM: Angiogenesis in malignancies of the female genital tract. Gynecol Oncol. 1999, 72: 220-231. 10.1006/gyno.1998.5152.CrossRefPubMed
17.
go back to reference Saravanamuthu J, Reid WM, George DS, Crow JC, Rolfe KJ, MacLean AB, Perrett CW: The role of angiogenesis in vulvar cancer, vulvar intraepithelial neoplasia, and vulvar lichen sclerosus as determined by microvessel density analysis. Gynecol Oncol. 2003, 89: 251-258. 10.1016/S0090-8258(03)00055-6.CrossRefPubMed Saravanamuthu J, Reid WM, George DS, Crow JC, Rolfe KJ, MacLean AB, Perrett CW: The role of angiogenesis in vulvar cancer, vulvar intraepithelial neoplasia, and vulvar lichen sclerosus as determined by microvessel density analysis. Gynecol Oncol. 2003, 89: 251-258. 10.1016/S0090-8258(03)00055-6.CrossRefPubMed
18.
go back to reference Bancher-Todesca D, Obermair A, Bilgi S, Kohlberger P, Kainz C, Breitenecker G, Leodolter S, Gitsch G: Angiogenesis in vulvar intraepithelial neoplasia. Gynecol Oncol. 1997, 64: 496-500. 10.1006/gyno.1996.4582.CrossRefPubMed Bancher-Todesca D, Obermair A, Bilgi S, Kohlberger P, Kainz C, Breitenecker G, Leodolter S, Gitsch G: Angiogenesis in vulvar intraepithelial neoplasia. Gynecol Oncol. 1997, 64: 496-500. 10.1006/gyno.1996.4582.CrossRefPubMed
19.
go back to reference Obermair A, Kohlberger P, Bancher-Todesca D, Tempfer C, Sliutz G, Leodolter S, Reinthaller A, Kainz C, Breitenecker G, Gitsch G: Influence of microvessel density and vascular permeability factor/vascular endothelial growth factor expression on prognosis in vulvar cancer. Gynecol Oncol. 1996, 63: 204-209. 10.1006/gyno.1996.0307.CrossRefPubMed Obermair A, Kohlberger P, Bancher-Todesca D, Tempfer C, Sliutz G, Leodolter S, Reinthaller A, Kainz C, Breitenecker G, Gitsch G: Influence of microvessel density and vascular permeability factor/vascular endothelial growth factor expression on prognosis in vulvar cancer. Gynecol Oncol. 1996, 63: 204-209. 10.1006/gyno.1996.0307.CrossRefPubMed
20.
go back to reference Qureshi F, Munkarah A, Banerjee M, Jacques SM: Tumor angiogenesis in vulvar squamous cell carcinoma. Gynecol Oncol. 1999, 72: 65-70. 10.1006/gyno.1998.5218.CrossRefPubMed Qureshi F, Munkarah A, Banerjee M, Jacques SM: Tumor angiogenesis in vulvar squamous cell carcinoma. Gynecol Oncol. 1999, 72: 65-70. 10.1006/gyno.1998.5218.CrossRefPubMed
21.
go back to reference Raspollini MR, Asirelli G, Taddei GL: The role of angiogenesis and COX-2 expression in the evolution of vulvar lichen sclerosus to squamous cell carcinoma of the vulva. Gynecol Oncol. 2007, 106: 567-571. 10.1016/j.ygyno.2007.05.007.CrossRefPubMed Raspollini MR, Asirelli G, Taddei GL: The role of angiogenesis and COX-2 expression in the evolution of vulvar lichen sclerosus to squamous cell carcinoma of the vulva. Gynecol Oncol. 2007, 106: 567-571. 10.1016/j.ygyno.2007.05.007.CrossRefPubMed
23.
go back to reference Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 1999, 59: 5830-5835.PubMed Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 1999, 59: 5830-5835.PubMed
24.
go back to reference Kimura S, Kitadai Y, Tanaka S, Kuwai T, Hihara J, Yoshida K, Toge T, Chayama K: Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma. Eur J Cancer. 2004, 40: 1904-1912. 10.1016/j.ejca.2004.04.035.CrossRefPubMed Kimura S, Kitadai Y, Tanaka S, Kuwai T, Hihara J, Yoshida K, Toge T, Chayama K: Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma. Eur J Cancer. 2004, 40: 1904-1912. 10.1016/j.ejca.2004.04.035.CrossRefPubMed
25.
go back to reference Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos C, Turley H, Talks K, Gatter KC, Harris AL: Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002, 53: 1192-1202. 10.1016/S0360-3016(02)02848-1.CrossRefPubMed Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos C, Turley H, Talks K, Gatter KC, Harris AL: Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002, 53: 1192-1202. 10.1016/S0360-3016(02)02848-1.CrossRefPubMed
26.
go back to reference Fillies T, Werkmeister R, van Diest PJ, Brandt B, Joos U, Buerger H: HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor. BMC Cancer. 2005, 5: 84-10.1186/1471-2407-5-84.CrossRefPubMedPubMedCentral Fillies T, Werkmeister R, van Diest PJ, Brandt B, Joos U, Buerger H: HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor. BMC Cancer. 2005, 5: 84-10.1186/1471-2407-5-84.CrossRefPubMedPubMedCentral
27.
go back to reference dos Santos M, Mercante AM, Louro ID, Goncalves AJ, de Carvalho MB, da Silva EH, da Silva AM: HIF1-alpha expression predicts survival of patients with squamous cell carcinoma of the oral cavity. PLoS One. 2012, 7: e45228-10.1371/journal.pone.0045228.CrossRefPubMedPubMedCentral dos Santos M, Mercante AM, Louro ID, Goncalves AJ, de Carvalho MB, da Silva EH, da Silva AM: HIF1-alpha expression predicts survival of patients with squamous cell carcinoma of the oral cavity. PLoS One. 2012, 7: e45228-10.1371/journal.pone.0045228.CrossRefPubMedPubMedCentral
28.
go back to reference Li YZ, Li SL, Li X, Wang LJ, Wang JL, Xu JW, Wu ZH, Gong L, Zhang XD: Expression of endogenous hypoxia markers in vulvar squamous cell carcinoma. Asian Pac J Cancer Prev. 2012, 13: 3675-3680. 10.7314/APJCP.2012.13.8.3675.CrossRefPubMed Li YZ, Li SL, Li X, Wang LJ, Wang JL, Xu JW, Wu ZH, Gong L, Zhang XD: Expression of endogenous hypoxia markers in vulvar squamous cell carcinoma. Asian Pac J Cancer Prev. 2012, 13: 3675-3680. 10.7314/APJCP.2012.13.8.3675.CrossRefPubMed
29.
go back to reference Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL: Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res. 2001, 61: 2911-2916.PubMed Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL: Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res. 2001, 61: 2911-2916.PubMed
30.
go back to reference Beasley NJ, Leek R, Alam M, Turley H, Cox GJ, Gatter K, Millard P, Fuggle S, Harris AL: Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 2002, 62: 2493-2497.PubMed Beasley NJ, Leek R, Alam M, Turley H, Cox GJ, Gatter K, Millard P, Fuggle S, Harris AL: Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 2002, 62: 2493-2497.PubMed
31.
go back to reference Hutchison GJ, Valentine HR, Loncaster JA, Davidson SE, Hunter RD, Roberts SA, Harris AL, Stratford IJ, Price PM, West CM: Hypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. Clin Cancer Res. 2004, 10: 8405-8412. 10.1158/1078-0432.CCR-03-0135.CrossRefPubMed Hutchison GJ, Valentine HR, Loncaster JA, Davidson SE, Hunter RD, Roberts SA, Harris AL, Stratford IJ, Price PM, West CM: Hypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. Clin Cancer Res. 2004, 10: 8405-8412. 10.1158/1078-0432.CCR-03-0135.CrossRefPubMed
32.
go back to reference Lin PY, Yu CH, Wang JT, Chen HH, Cheng SJ, Kuo MY, Chiang CP: Expression of hypoxia-inducible factor-1 alpha is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan. J Oral Pathol Med. 2008, 37: 18-25.CrossRefPubMed Lin PY, Yu CH, Wang JT, Chen HH, Cheng SJ, Kuo MY, Chiang CP: Expression of hypoxia-inducible factor-1 alpha is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan. J Oral Pathol Med. 2008, 37: 18-25.CrossRefPubMed
33.
go back to reference Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med. 2003, 9: 669-676. 10.1038/nm0603-669.CrossRefPubMed Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med. 2003, 9: 669-676. 10.1038/nm0603-669.CrossRefPubMed
34.
go back to reference Jubb AM, Pham TQ, Hanby AM, Frantz GD, Peale FV, Wu TD, Koeppen HW, Hillan KJ: Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. J Clin Pathol. 2004, 57: 504-512. 10.1136/jcp.2003.012963.CrossRefPubMedPubMedCentral Jubb AM, Pham TQ, Hanby AM, Frantz GD, Peale FV, Wu TD, Koeppen HW, Hillan KJ: Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. J Clin Pathol. 2004, 57: 504-512. 10.1136/jcp.2003.012963.CrossRefPubMedPubMedCentral
35.
go back to reference Doldi N, Origoni M, Bassan M, Ferrari D, Rossi M, Ferrari A: Vascular endothelial growth factor. Expression in human vulvar neoplastic and nonneoplastic tissues. J Reprod Med. 1996, 41: 844-848.PubMed Doldi N, Origoni M, Bassan M, Ferrari D, Rossi M, Ferrari A: Vascular endothelial growth factor. Expression in human vulvar neoplastic and nonneoplastic tissues. J Reprod Med. 1996, 41: 844-848.PubMed
36.
go back to reference Knopp S, Trope C, Nesland JM, Holm R: A review of molecular pathological markers in vulvar carcinoma: lack of application in clinical practice. J Clin Pathol. 2009, 62: 212-218. 10.1136/jcp.2008.057240.CrossRefPubMed Knopp S, Trope C, Nesland JM, Holm R: A review of molecular pathological markers in vulvar carcinoma: lack of application in clinical practice. J Clin Pathol. 2009, 62: 212-218. 10.1136/jcp.2008.057240.CrossRefPubMed
37.
go back to reference Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009, 105: 103-104. 10.1016/j.ijgo.2009.02.012.CrossRefPubMed Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009, 105: 103-104. 10.1016/j.ijgo.2009.02.012.CrossRefPubMed
38.
go back to reference Wilkinson EJaTMR: Tumours of the vulva. Epithelial tumours. World Health Organization Classification of Tumours. Pathology and genetics of tumors of the breast and female genital organs. Edited by: Tavassoli FA, Devilee P. 2003, Lyon: ARC Press, 316-325. Wilkinson EJaTMR: Tumours of the vulva. Epithelial tumours. World Health Organization Classification of Tumours. Pathology and genetics of tumors of the breast and female genital organs. Edited by: Tavassoli FA, Devilee P. 2003, Lyon: ARC Press, 316-325.
39.
go back to reference Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van ME, Magnani E, Weidner N, Harris AL, Dirix LY: Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002, 38: 1564-1579. 10.1016/S0959-8049(02)00094-1.CrossRefPubMed Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van ME, Magnani E, Weidner N, Harris AL, Dirix LY: Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002, 38: 1564-1579. 10.1016/S0959-8049(02)00094-1.CrossRefPubMed
40.
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: 1-8. 10.1056/NEJM199101033240101.CrossRefPubMed Weidner N, Semple JP, Welch WR, Folkman J: Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med. 1991, 324: 1-8. 10.1056/NEJM199101033240101.CrossRefPubMed
41.
go back to reference Binder SW, Huang I, Fu YS, Hacker NF, Berek JS: Risk factors for the development of lymph node metastasis in vulvar squamous cell carcinoma. Gynecol Oncol. 1990, 37: 9-16. 10.1016/0090-8258(90)90298-Y.CrossRefPubMed Binder SW, Huang I, Fu YS, Hacker NF, Berek JS: Risk factors for the development of lymph node metastasis in vulvar squamous cell carcinoma. Gynecol Oncol. 1990, 37: 9-16. 10.1016/0090-8258(90)90298-Y.CrossRefPubMed
42.
go back to reference der SS V, De Nieuwenhof HP, Massuger L, Bulten J, De Hullu JA: New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis. Gynecol Oncol. 2010, 119: 520-525. 10.1016/j.ygyno.2010.08.036.CrossRef der SS V, De Nieuwenhof HP, Massuger L, Bulten J, De Hullu JA: New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis. Gynecol Oncol. 2010, 119: 520-525. 10.1016/j.ygyno.2010.08.036.CrossRef
43.
go back to reference Woelber L, Eulenburg C, Choschzick M, Kruell A, Petersen C, Gieseking F, Jaenicke F, Mahner S: Prognostic role of lymph node metastases in vulvar cancer and implications for adjuvant treatment. Int J Gynecol Cancer. 2012, 22: 503-508. 10.1097/IGC.0b013e31823eed4c.CrossRefPubMed Woelber L, Eulenburg C, Choschzick M, Kruell A, Petersen C, Gieseking F, Jaenicke F, Mahner S: Prognostic role of lymph node metastases in vulvar cancer and implications for adjuvant treatment. Int J Gynecol Cancer. 2012, 22: 503-508. 10.1097/IGC.0b013e31823eed4c.CrossRefPubMed
44.
go back to reference Woelber L, Mahner S, Voelker K, Eulenburg CZ, Gieseking F, Choschzick M, Jaenicke F, Schwarz J: Clinicopathological prognostic factors and patterns of recurrence in vulvar cancer. Anticancer Res. 2009, 29: 545-552.PubMed Woelber L, Mahner S, Voelker K, Eulenburg CZ, Gieseking F, Choschzick M, Jaenicke F, Schwarz J: Clinicopathological prognostic factors and patterns of recurrence in vulvar cancer. Anticancer Res. 2009, 29: 545-552.PubMed
45.
go back to reference Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL: Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol. 1995, 177: 275-283. 10.1002/path.1711770310.CrossRefPubMed Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL: Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol. 1995, 177: 275-283. 10.1002/path.1711770310.CrossRefPubMed
46.
go back to reference Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G: Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000, 60: 4693-4696.PubMed Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G: Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000, 60: 4693-4696.PubMed
47.
go back to reference Shibata-Kobayashi S, Yamashita H, Okuma K, Shiraishi K, Igaki H, Ohtomo K, Nakagawa K: Correlation among 16 biological factors [p53, p21(waf1), MIB-1 (Ki-67), p16(INK4A), cyclin D1, E-cadherin, Bcl-2, TNF-alpha, NF-kappaB, TGF-beta, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1alpha] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma. Oncol Lett. 2013, 5: 903-910.PubMedPubMedCentral Shibata-Kobayashi S, Yamashita H, Okuma K, Shiraishi K, Igaki H, Ohtomo K, Nakagawa K: Correlation among 16 biological factors [p53, p21(waf1), MIB-1 (Ki-67), p16(INK4A), cyclin D1, E-cadherin, Bcl-2, TNF-alpha, NF-kappaB, TGF-beta, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1alpha] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma. Oncol Lett. 2013, 5: 903-910.PubMedPubMedCentral
48.
go back to reference Keith B, Johnson RS, Simon MC: HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2012, 12: 9-22. Keith B, Johnson RS, Simon MC: HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2012, 12: 9-22.
49.
go back to reference Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, Yu KT, Jaye M, Ivashchenko Y: Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ. 2001, 8: 367-376. 10.1038/sj.cdd.4400810.CrossRefPubMed Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, Yu KT, Jaye M, Ivashchenko Y: Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ. 2001, 8: 367-376. 10.1038/sj.cdd.4400810.CrossRefPubMed
50.
go back to reference Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL: HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 2001, 61: 6669-6673.PubMed Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL: HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 2001, 61: 6669-6673.PubMed
51.
go back to reference Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M: Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell. 2010, 140: 268-279. 10.1016/j.cell.2009.12.046.CrossRefPubMed Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M: Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell. 2010, 140: 268-279. 10.1016/j.cell.2009.12.046.CrossRefPubMed
52.
go back to reference Cao Y, Ei G, Wang E, Pal K, Dutta SK, Bar-Sagi D, Mukhopadhyay D: VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression. Cancer Res. 2012, 72: 3912-3918. 10.1158/0008-5472.CAN-11-4058.CrossRefPubMedPubMedCentral Cao Y, Ei G, Wang E, Pal K, Dutta SK, Bar-Sagi D, Mukhopadhyay D: VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression. Cancer Res. 2012, 72: 3912-3918. 10.1158/0008-5472.CAN-11-4058.CrossRefPubMedPubMedCentral
53.
go back to reference Yoshiji H, Harris SR, Thorgeirsson UP: Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res. 1997, 57: 3924-3928.PubMed Yoshiji H, Harris SR, Thorgeirsson UP: Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res. 1997, 57: 3924-3928.PubMed
54.
go back to reference Cao Y, Li CY, Moeller BJ, Yu D, Zhao Y, Dreher MR, Shan S, Dewhirst MW: Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. Cancer Res. 2005, 65: 5498-5505. 10.1158/0008-5472.CAN-04-4553.CrossRefPubMed Cao Y, Li CY, Moeller BJ, Yu D, Zhao Y, Dreher MR, Shan S, Dewhirst MW: Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. Cancer Res. 2005, 65: 5498-5505. 10.1158/0008-5472.CAN-04-4553.CrossRefPubMed
55.
go back to reference Mighell AJ, Hume WJ, Robinson PA: An overview of the complexities and subtleties of immunohistochemistry. Oral Dis. 1998, 4: 217-223.CrossRefPubMed Mighell AJ, Hume WJ, Robinson PA: An overview of the complexities and subtleties of immunohistochemistry. Oral Dis. 1998, 4: 217-223.CrossRefPubMed
56.
go back to reference Skaland I, Nordhus M, Gudlaugsson E, Klos J, Kjellevold KH, Janssen EA, Baak JP: Evaluation of 5 different labeled polymer immunohistochemical detection systems. Appl Immunohistochem Mol Morphol. 2010, 18: 90-96. 10.1097/PAI.0b013e3181b0eaad.CrossRefPubMed Skaland I, Nordhus M, Gudlaugsson E, Klos J, Kjellevold KH, Janssen EA, Baak JP: Evaluation of 5 different labeled polymer immunohistochemical detection systems. Appl Immunohistochem Mol Morphol. 2010, 18: 90-96. 10.1097/PAI.0b013e3181b0eaad.CrossRefPubMed
57.
go back to reference Warren MV, Chan WY, Ridley JM: Analysis of protein biomarkers in human clinical tumor samples: critical aspects to success from tissue acquisition to analysis. Biomark Med. 2011, 5: 227-248. 10.2217/bmm.11.9.CrossRefPubMed Warren MV, Chan WY, Ridley JM: Analysis of protein biomarkers in human clinical tumor samples: critical aspects to success from tissue acquisition to analysis. Biomark Med. 2011, 5: 227-248. 10.2217/bmm.11.9.CrossRefPubMed
Metadata
Title
Primary Tumor Vascularity, HIF-1α and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact
Authors
Hari Prasad Dhakal
Jahn M Nesland
Mette Førsund
Claes G Trope
Ruth Holm
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-506

Other articles of this Issue 1/2013

BMC Cancer 1/2013 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