The prognostic value of microvascular density in lung carcinomas

The prognostic value of microvascular density in lung carcinomas

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Title: The prognostic value of microvascular density in lung carcinomas
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Article_Title: The prognostic value of microvascular density in lung carcinomas
Authors: Amalia Birau, Raluca Amalia Ceausu, Anca Maria Cimpean, Pusa Gaje, Stefana Feflea, Gheorghe Ciobanu, Teodora Olariu, Marius Raica
Affiliation: 1Department of Intensive Care*, Department of Radiology **„Vasile Goldis” Western University of Arad
2”Victor Babes” University of Medicine and Pharmacy, Department of Histology, Angiogenesis Research
Center Timisoara, Romania
Abstract: As one of the first quantifiable methods used in the study of angiogenesis, microvascualar density was performed to all currently known tumors, including lung cancer. There are still numerous controversies regarding the prognostic value of microvascular density. For these reasons, the aim of this study was to investigate the morphology and the density of blood vessels in different pathological types of lung carcinomas using CD34 as antibody. We have included in our study 42 patients. In small cell lung carcinomas, CD34-positive vessels were significantly less in comparison with adenocarcinomas. The peritumoral vessels were significantly more numerous than the intratumoral, excepting for large cell lung carcinomas. The lowest values of microvascular density were found for small cell lung carcinomas. We found statistically significant correlation between microvascular density, tumor stage (p<0.00021) and the degree of differentiation (p<0.0032). Although MVD can be a useful prognostic element, there are enough data to support its role for assessing efficiency of anti-angiogenic therapy.
Keywords: angiogenesis, microvascular density, lung carcinomas, prognosis
References: Gazdar AF, Minna JD, Angiogenesis and the Multistage Development of Lung Cancers. Clin Cancer Res., 6(5), 1611-1612, 2000.
Aikawa H, Takahashi H, Fujimura S, Sato M, Endo C, Sakurada A, Kondo T, Tanita T, Matsumura Y, Ono S, Saito Y, Sagawa M, Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer. Anticancer Res., 19(5B), 4305-4309, 1999.
Carlini MJ, Dalurzo MC, Lastiri JM, Smith DE, Vasallo BC, Puricelli LI, Lauría de Cidre LS, Mast cell phenotypes and microvessels in non–small cell lung cancer and its prognostic significance. Hum Pathol., 41(5), 697-705, 2010.
Cox G, Jones JL, Andi A, Waller DA, O’Byrne KJ, A biological staging model for operable non-small cell lung cancer. Thorax, 56, 561–566, 2001.
Chandrachud LM, Pendleton N, Chisholm DM, Horan MA, Schor AM, Relationship between vascularity, age and survival in non-small-cell lung cancer. Br J Cancer,76, 1367–1375, 1997.
Dazzi C, Cariello A, Maioli P, Solaini L, Scarpi E, Rosti G, Lanzanova G, Marangolo M, Prognostic and predictive value of intratumoral microvessels density in operable non-small-cell lung cancer. Lung Cancer, 24, 81-88, 1999.
de Jong JS, van Diest PJ, Baak JP, Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer. Histopathology, 36(4), 306-312, 2000.
Folkman J, Merler E, Abernathy C, Williams G, Isolation of a tumor factor responsible for angiogenesis. J Exp Med., 133, 275-288, 1971.
Fontanini G, Calcinai A, Boldrini L, Lucchi M, Mussi A, Angeletti CA, Cagno C, Tognetti MA, Basolo F, Modulation of neoangiogenesis in bronchial preneoplastic lesions. Oncol. Rep., 6, 813-817, 1999.
Fontanini G, Lucchi M, Vignati S, et al., Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study. J Natl Cancer Inst., 89, 881–886, 1997.
Ge G, Zhou Q, Zhang S, Liu L, Chen J, Cheng N, Qin J, Li L, Detection of micro-vascular density(MVD) and its clinical significance in lung cancer. Zhongguo Fei Ai Za Zhi., 3(4), 284-287, 2000.
Giatromanolaki A, Koukourakis MI, Theodossiou D, et al., Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer. Clin Cancer Res., 3, 2485–2492, 1997.
.Hanahan D, Folkman J., Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell., 86, 353–364, 1996.
Iakovlev V, Gabril M, Dubinski W, Scorilas A, Youssef M, Faragalla H, Kovacs K, Rotondo F, Metias S, Arsanious A, Plotkin A, Girgis A, Streutker CJ, Microvascular Density as an Independent Predictor of Clinical Outcome in Renal Cell Carcinoma An Automated Image Analysis Study. Laboratory Investigation, 92(1), 46-56, 2012.
Liao M, Wang H, Lin Z, Feng J, Zhu D, Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer. Lung Cancer, 33, 125–132, 2001.
Maeda R, Ishii G, Ito M, Hishida T, Yoshida J, Nishimura M, Haga H, Nagai K, Ochiai A, Number of Circulating Endothelial Progenitor Cells and Intratumoral Microvessel Density in Non-small Cell Lung Cancer Patients: Differences in Angiogenic
Status between Adenocarcinoma Histologic Subtypes. J Thorac Oncol., Epub ahead of print Dec 22, 2011.
O’Byrne KJ, Koukourakis MI, Giatromanolaki A, et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer, 82, 1427–1432, 2000.
Ozbudak IH, Ozbilim G, Kucukosmanoglu I, Dertsiz L, Demircan A, Vascular endothelial growth factor expression and neovascularization in non–small cell lung carcinoma. Int J Surg Pathol., 17(5), 390-395, 2009.
Pastorino U, Andreola S, Tagliabue E, et al., Immunocytochemical markers in stage I lung cancer: relevance to prognosis. J Clin Oncol., 15, 2858–2865, 1997.
Schor AM, Pazouki S, Morris J, Smither RL, Chandrachud LM, Pendleton N, Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus. Br J Cancer., 77(6), 946–951, 1998.
Weidner N., Tumoral vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol.,184, 119–122, 1998.
Zhao YY, Xue C, Jiang W, Zhao HY, Huang Y, Feenstra K, Resau JH, Qian CN, Zhang L, Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. J Thorac Oncol., 7(1), 71-75, 2012.
Read_full_article: pdf/22-2012/22-1-2012/SU22-1-2012-Birau1.pdf
Correspondence: Amalia Birau, MD, PhD student, Department of Intensive Care, „Vasile Goldis” Western University of Arad, no.1 Feleacului St., Arad, Romania, Tel: +40-257-212204; birauamalia@yahoo.com

Read full article
Article Title: The prognostic value of microvascular density in lung carcinomas
Authors: Amalia Birau, Raluca Amalia Ceausu, Anca Maria Cimpean, Pusa Gaje, Stefana Feflea, Gheorghe Ciobanu, Teodora Olariu, Marius Raica
Affiliation: 1Department of Intensive Care*, Department of Radiology **„Vasile Goldis” Western University of Arad
2”Victor Babes” University of Medicine and Pharmacy, Department of Histology, Angiogenesis Research
Center Timisoara, Romania
Abstract: As one of the first quantifiable methods used in the study of angiogenesis, microvascualar density was performed to all currently known tumors, including lung cancer. There are still numerous controversies regarding the prognostic value of microvascular density. For these reasons, the aim of this study was to investigate the morphology and the density of blood vessels in different pathological types of lung carcinomas using CD34 as antibody. We have included in our study 42 patients. In small cell lung carcinomas, CD34-positive vessels were significantly less in comparison with adenocarcinomas. The peritumoral vessels were significantly more numerous
than the intratumoral, excepting for large cell lung carcinomas. The lowest values of microvascular density were found for small cell lung carcinomas. We found statistically significant correlation between microvascular density, tumor stage (p<0.00021) and the degree of differentiation (p<0.0032). Although MVD can be a useful prognostic element, there are enough data to support its role for assessing efficiency of anti-angiogenic therapy.
Keywords: angiogenesis, microvascular density, lung carcinomas, prognosis
References: Gazdar AF, Minna JD, Angiogenesis and the Multistage Development of Lung Cancers. Clin Cancer Res., 6(5), 1611-1612, 2000.
Aikawa H, Takahashi H, Fujimura S, Sato M, Endo C, Sakurada A, Kondo T, Tanita T, Matsumura Y, Ono S, Saito Y, Sagawa M, Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer. Anticancer Res., 19(5B), 4305-4309, 1999.
Carlini MJ, Dalurzo MC, Lastiri JM, Smith DE, Vasallo BC, Puricelli LI, Lauría de Cidre LS, Mast cell phenotypes and microvessels in non–small cell lung cancer and its prognostic significance. Hum Pathol., 41(5), 697-705, 2010.
Cox G, Jones JL, Andi A, Waller DA, O’Byrne KJ, A biological staging model for operable non-small cell lung cancer. Thorax, 56, 561–566, 2001.
Chandrachud LM, Pendleton N, Chisholm DM, Horan MA, Schor AM, Relationship between vascularity, age and survival in non-small-cell lung cancer. Br J Cancer,76, 1367–1375, 1997.
Dazzi C, Cariello A, Maioli P, Solaini L, Scarpi E, Rosti G, Lanzanova G, Marangolo M, Prognostic and predictive value of intratumoral microvessels density in operable non-small-cell lung cancer. Lung Cancer, 24, 81-88, 1999.
de Jong JS, van Diest PJ, Baak JP, Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer. Histopathology, 36(4), 306-312, 2000.
Folkman J, Merler E, Abernathy C, Williams G, Isolation of a tumor factor responsible for angiogenesis. J Exp Med., 133, 275-288, 1971.
Fontanini G, Calcinai A, Boldrini L, Lucchi M, Mussi A, Angeletti CA, Cagno C, Tognetti MA, Basolo F, Modulation of neoangiogenesis in bronchial preneoplastic lesions. Oncol. Rep., 6, 813-817, 1999.
Fontanini G, Lucchi M, Vignati S, et al., Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study. J Natl Cancer Inst., 89, 881–886, 1997.
Ge G, Zhou Q, Zhang S, Liu L, Chen J, Cheng N, Qin J, Li L, Detection of micro-vascular density(MVD) and its clinical significance in lung cancer. Zhongguo Fei Ai Za Zhi., 3(4), 284-287, 2000.
Giatromanolaki A, Koukourakis MI, Theodossiou D, et al., Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer. Clin Cancer Res., 3, 2485–2492, 1997.
.Hanahan D, Folkman J., Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell., 86, 353–364, 1996.
Iakovlev V, Gabril M, Dubinski W, Scorilas A, Youssef M, Faragalla H, Kovacs K, Rotondo F, Metias S, Arsanious A, Plotkin A, Girgis A, Streutker CJ, Microvascular Density as an Independent Predictor of Clinical Outcome in Renal Cell Carcinoma An Automated Image Analysis Study. Laboratory Investigation, 92(1), 46-56, 2012.
Liao M, Wang H, Lin Z, Feng J, Zhu D, Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer. Lung Cancer, 33, 125–132, 2001.
Maeda R, Ishii G, Ito M, Hishida T, Yoshida J, Nishimura M, Haga H, Nagai K, Ochiai A, Number of Circulating Endothelial Progenitor Cells and Intratumoral Microvessel Density in Non-small Cell Lung Cancer Patients: Differences in Angiogenic
Status between Adenocarcinoma Histologic Subtypes. J Thorac Oncol., Epub ahead of print Dec 22, 2011.
O’Byrne KJ, Koukourakis MI, Giatromanolaki A, et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer, 82, 1427–1432, 2000.
Ozbudak IH, Ozbilim G, Kucukosmanoglu I, Dertsiz L, Demircan A, Vascular endothelial growth factor expression and neovascularization in non–small cell lung carcinoma. Int J Surg Pathol., 17(5), 390-395, 2009.
Pastorino U, Andreola S, Tagliabue E, et al., Immunocytochemical markers in stage I lung cancer: relevance to prognosis. J Clin Oncol., 15, 2858–2865, 1997.
Schor AM, Pazouki S, Morris J, Smither RL, Chandrachud LM, Pendleton N, Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus. Br J Cancer., 77(6), 946–951, 1998.
Weidner N., Tumoral vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol.,184, 119–122, 1998.
Zhao YY, Xue C, Jiang W, Zhao HY, Huang Y, Feenstra K, Resau JH, Qian CN, Zhang L, Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. J Thorac Oncol., 7(1), 71-75, 2012.
*Correspondence: Amalia Birau, MD, PhD student, Department of Intensive Care, „Vasile Goldis” Western University of Arad, no.1 Feleacului St., Arad, Romania, Tel: +40-257-212204; birauamalia@yahoo.com