Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Microvessel density as new prognostic marker after radiotherapy in rectal cancer

Authors: Saulius Svagzdys, Vaiva Lesauskaite, Dainius Pavalkis, Irena Nedzelskienė, Darius Pranys, Algimantas Tamelis

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

The extent of angiogenesis is an important prognostic factor for colorectal carcinoma, however, there are few studies concerning changes in angiogenesis with radiotherapy (RTX). Our aim was to investigate changes in tumor angiogenesis influenced by radiotherapy to assess the prognostic value of angiogenesis the microvessel density (MVD) in overall survival after radiotherapy.

Methods

Tumor specimens were taken from 101 patients resected for rectal cancer. The patients were divided into three groups according to the treatment they received before surgery (not treated, a short course, or long course of RTX). Tumor specimens were paraffin-embedded and immunohistochemistry was performed with primary antibody against CD-34 to count MVD.

Results

MVD was significantly lower in the group of patients treated with a long course of RTX (p <0.025). The mean MVD for the long RTX group was 134.8; for the short RTX group – 192.5; and for those not treated with RTX – 193.0. There were no significant statistical correlations between MVD and age, sex, grade of tumor differentiation (G) and tumor size (T) in those untreated with RTX. In long RTX group we found a significant prognostic rate for MVD when the density cut off was near 130 with 92.3% sensitivity and 64.7% specificity. When the MVD was lower than a cut off of 130, the survival period significantly increased (p = 0.001), the mortality rate is significantly higher if the MVD is higher than 130 (microvessel/mm2) (1953.047; p = 0.002), if the histological grade is moderate/poor (127.407; p = 0.013), if the tumor is T3/T4 (111.618; p = 0.014), and if the patient is male (17.92; p = 0.034) adjusted by other variable in model.

Conclusion

Our results show that a long course of radiotherapy significantly decreased angiogenesis in rectal cancer tissue. MVD was found to be a favourable marker for tumor behaviour during RTX and a predictor of overall survival after long course of RTX. Further investigations are now needed to determine the changes in angiogenesis during a shorter course of RTX.
Appendix
Available only for authorised users
Literature
1.
go back to reference Des GG, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al: Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer. 2006, 94: 1823-1832. 10.1038/sj.bjc.6603176.CrossRef Des GG, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al: Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer. 2006, 94: 1823-1832. 10.1038/sj.bjc.6603176.CrossRef
2.
go back to reference Latkauskas T, Rudinskaite G, Kurtinaitis J, Janciauskiene R, Tamelis A, Saladzinskas Z, et al: The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment. BMC Cancer. 2005, 5: 153-10.1186/1471-2407-5-153.CrossRefPubMedPubMedCentral Latkauskas T, Rudinskaite G, Kurtinaitis J, Janciauskiene R, Tamelis A, Saladzinskas Z, et al: The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment. BMC Cancer. 2005, 5: 153-10.1186/1471-2407-5-153.CrossRefPubMedPubMedCentral
3.
go back to reference Jass JR: Pathogenesis of colorectal cancer. Surg Clin North Am. 2002, 82: 891-904. 10.1016/S0039-6109(02)00047-6.CrossRefPubMed Jass JR: Pathogenesis of colorectal cancer. Surg Clin North Am. 2002, 82: 891-904. 10.1016/S0039-6109(02)00047-6.CrossRefPubMed
4.
go back to reference Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001, 345: 638-646. 10.1056/NEJMoa010580.CrossRefPubMed Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001, 345: 638-646. 10.1056/NEJMoa010580.CrossRefPubMed
5.
go back to reference Ortholan C, Francois E, Thomas O, Benchimol D, Baulieux J, Bosset JF, et al: Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum. 2006, 49: 302-310. 10.1007/s10350-005-0263-x.CrossRefPubMed Ortholan C, Francois E, Thomas O, Benchimol D, Baulieux J, Bosset JF, et al: Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum. 2006, 49: 302-310. 10.1007/s10350-005-0263-x.CrossRefPubMed
6.
go back to reference Bendardaf R, Lamlum H, Pyrhonen S: Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res. 2004, 24: 2519-2530.PubMed Bendardaf R, Lamlum H, Pyrhonen S: Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res. 2004, 24: 2519-2530.PubMed
7.
go back to reference Sun XF, Zhang H: Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol Cancer. 2006, 5: 43-10.1186/1476-4598-5-43.CrossRefPubMedPubMedCentral Sun XF, Zhang H: Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol Cancer. 2006, 5: 43-10.1186/1476-4598-5-43.CrossRefPubMedPubMedCentral
8.
go back to reference Duff SE, Jeziorska M, Kumar S, Haboubi N, Sherlock D, O'Dwyer ST, et al: Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer. Colorectal Dis. 2007, 9: 793-800. 10.1111/j.1463-1318.2006.01199.x.CrossRefPubMed Duff SE, Jeziorska M, Kumar S, Haboubi N, Sherlock D, O'Dwyer ST, et al: Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer. Colorectal Dis. 2007, 9: 793-800. 10.1111/j.1463-1318.2006.01199.x.CrossRefPubMed
9.
go back to reference Fleming ID CJHDHRKBMGeale: AJCC cancer staging manual. 1997, Philadelphia: J.B.Lippincott, 5 Fleming ID CJHDHRKBMGeale: AJCC cancer staging manual. 1997, Philadelphia: J.B.Lippincott, 5
10.
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.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.CrossRefPubMed
11.
go back to reference Kumar A, Collins HM, Scholefield JH, Watson SA: Increased type-IV collagenase (MMP-2 and MMP-9) activity following preoperative radiotherapy in rectal cancer. Br J Cancer. 2000, 82: 960-965. 10.1054/bjoc.1999.1025.CrossRefPubMedPubMedCentral Kumar A, Collins HM, Scholefield JH, Watson SA: Increased type-IV collagenase (MMP-2 and MMP-9) activity following preoperative radiotherapy in rectal cancer. Br J Cancer. 2000, 82: 960-965. 10.1054/bjoc.1999.1025.CrossRefPubMedPubMedCentral
12.
go back to reference Stanciute D, Didziapetriene J, Kadziauskas J: [Expression of matrix metalloproteinases in patients with malignant tumors]. Medicina (Kaunas). 2004, 40: 1143-1150. Stanciute D, Didziapetriene J, Kadziauskas J: [Expression of matrix metalloproteinases in patients with malignant tumors]. Medicina (Kaunas). 2004, 40: 1143-1150.
13.
go back to reference Wang JL, Sun Y, Wu S: Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner. Mol Carcinog. 2000, 27: 252-258. 10.1002/(SICI)1098-2744(200004)27:4<252::AID-MC2>3.0.CO;2-3.CrossRefPubMed Wang JL, Sun Y, Wu S: Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner. Mol Carcinog. 2000, 27: 252-258. 10.1002/(SICI)1098-2744(200004)27:4<252::AID-MC2>3.0.CO;2-3.CrossRefPubMed
14.
go back to reference Speake WJ, Dean RA, Kumar A, Morris TM, Scholefield JH, Watson SA: Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion. Eur J Surg Oncol. 2005, 31: 869-874. 10.1016/j.ejso.2005.05.016.CrossRefPubMed Speake WJ, Dean RA, Kumar A, Morris TM, Scholefield JH, Watson SA: Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion. Eur J Surg Oncol. 2005, 31: 869-874. 10.1016/j.ejso.2005.05.016.CrossRefPubMed
15.
go back to reference Baeten CI, Castermans K, Lammering G, Hillen F, Wouters BG, Hillen HF, et al: Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer. Int J Radiat Oncol Biol Phys. 2006, 66: 1219-1227.CrossRefPubMed Baeten CI, Castermans K, Lammering G, Hillen F, Wouters BG, Hillen HF, et al: Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer. Int J Radiat Oncol Biol Phys. 2006, 66: 1219-1227.CrossRefPubMed
16.
go back to reference Gaugler MH, Squiban C, van der MA, Bertho JM, Vandamme M, Mouthon MA: Late and persistent up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression by ionizing radiation in human endothelial cells in vitro. Int J Radiat Biol. 1997, 72: 201-209. 10.1080/095530097143428.CrossRefPubMed Gaugler MH, Squiban C, van der MA, Bertho JM, Vandamme M, Mouthon MA: Late and persistent up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression by ionizing radiation in human endothelial cells in vitro. Int J Radiat Biol. 1997, 72: 201-209. 10.1080/095530097143428.CrossRefPubMed
17.
go back to reference Kissane JH: Anderson's Pathology. 1990, St.Louis, Baltimore, Philadelphia, Toronto: The CV Mosby Company, 9 Kissane JH: Anderson's Pathology. 1990, St.Louis, Baltimore, Philadelphia, Toronto: The CV Mosby Company, 9
18.
go back to reference Angenete E, Langenskiold M, Falk P, Ivarsson ML: Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation. Int J Colorectal Dis. 2007, 22: 667-674. 10.1007/s00384-006-0225-3.CrossRefPubMed Angenete E, Langenskiold M, Falk P, Ivarsson ML: Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation. Int J Colorectal Dis. 2007, 22: 667-674. 10.1007/s00384-006-0225-3.CrossRefPubMed
19.
go back to reference Nirmala C, Jasti SL, Sawaya R, Kyritsis AP, Konduri SD, Ali-Osman F, et al: Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions. Int J Cancer. 2000, 88: 766-771. 10.1002/1097-0215(20001201)88:5<766::AID-IJC13>3.0.CO;2-Y.CrossRefPubMed Nirmala C, Jasti SL, Sawaya R, Kyritsis AP, Konduri SD, Ali-Osman F, et al: Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions. Int J Cancer. 2000, 88: 766-771. 10.1002/1097-0215(20001201)88:5<766::AID-IJC13>3.0.CO;2-Y.CrossRefPubMed
20.
go back to reference Gallego MG: Vascular enumeration as a prognosticator for colorectal carcinoma. European Journal of Cance. 2000, 36: 55-60. 10.1016/S0959-8049(99)00243-9.CrossRef Gallego MG: Vascular enumeration as a prognosticator for colorectal carcinoma. European Journal of Cance. 2000, 36: 55-60. 10.1016/S0959-8049(99)00243-9.CrossRef
21.
go back to reference Zheng S, Han MY, Xiao ZX, Peng JP, Dong Q: Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma. World J Gastroenterol. 2003, 9: 1227-1230.CrossRefPubMedPubMedCentral Zheng S, Han MY, Xiao ZX, Peng JP, Dong Q: Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma. World J Gastroenterol. 2003, 9: 1227-1230.CrossRefPubMedPubMedCentral
22.
go back to reference Shia J, Guillem JG, Moore HG, Tickoo SK, Qin J, Ruo L, et al: Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol. 2004, 28: 215-223. 10.1097/00000478-200402000-00009.CrossRefPubMed Shia J, Guillem JG, Moore HG, Tickoo SK, Qin J, Ruo L, et al: Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol. 2004, 28: 215-223. 10.1097/00000478-200402000-00009.CrossRefPubMed
Metadata
Title
Microvessel density as new prognostic marker after radiotherapy in rectal cancer
Authors
Saulius Svagzdys
Vaiva Lesauskaite
Dainius Pavalkis
Irena Nedzelskienė
Darius Pranys
Algimantas Tamelis
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-95

Other articles of this Issue 1/2009

BMC Cancer 1/2009 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