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Published in: Annals of Surgical Oncology 6/2009

01-06-2009 | Thoracic Oncology

D2-40-Positive Lymphatic Vessel Density Is a Poor Prognostic Factor in Squamous Cell Carcinoma of the Lung

Authors: Shotaro Iwakiri, MD, Shinjiro Nagai, PhD, MD, Hiromichi Katakura, PhD, MD, Kazumasa Takenaka, PhD, MD, Hiroshi Date, PhD, MD, Hiromi Wada, PhD, MD, Fumihiro Tanaka, PhD, MD

Published in: Annals of Surgical Oncology | Issue 6/2009

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Abstract

Background

Experimental studies have revealed that D2-40 is useful in identifying the presence of lymphatic invasion in various malignant neoplasms, but the clinical significance remains unclear. The purpose of this study is to assess the clinical significance of D2-40 status in completely resected non–small cell lung cancer.

Methods

A total of 215 consecutive patients with resected pathological stage I–IIIA non–small cell lung cancer were reviewed. Expression of D2-40 in tumor cells and in endothelial cells was examined immunohistochemically, and D2-40-positive lymphatic vessel density (LVD) at the tumor periphery were quantitatively evaluated.

Results

D2-40 expression on tumor cells was positive in 55 (25.6%) of 215 patients, and the incidence was significantly higher in squamous cell carcinoma (SCC) patients than in adenocarcinoma patients (48.8% vs. 8.6%, P < .001). D2-40 was also seen on lymphatic vessels in tumor tissues, and the mean number of D2-40-LVD was significantly decreased along with differentiation of tumor cells (P = .038). For all histologic types of tumors, there was no difference in the postoperative survival between higher D2-40-LVD patients and lower D2-40-LVD patients. For SCC, however, lower D2-40-LVD patients showed a significantly better survival than higher D2-40-LVD patients (5-year survival rates, 52.9% vs. 78.9%, P = .040), which was confirmed by a multivariate analyses (P = .048).

Conclusions

D2-40 expression on tumor cells was more frequently seen in SCC than in adenocarcinoma of the lung. In addition, D2-40 expression on lymphatic vessels in tumor tissues was a statistically significant prognostic factor in SCC.
Literature
1.
go back to reference Pearson FG. Non-small cell lung cancer: role of surgery for stages I–III. Chest. 1999;116:500–3.CrossRef Pearson FG. Non-small cell lung cancer: role of surgery for stages I–III. Chest. 1999;116:500–3.CrossRef
2.
go back to reference Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef
3.
go back to reference Marks A, Sutherland DR, Bailey D, et al. Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer. 1999;80:569–78.PubMedCrossRef Marks A, Sutherland DR, Bailey D, et al. Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer. 1999;80:569–78.PubMedCrossRef
4.
go back to reference Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434–40.PubMedCrossRef Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434–40.PubMedCrossRef
5.
go back to reference Franke FE, Steger K, Marks A, Kutzner H, Mentzel T. Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas. J Cutan Pathol. 2004;31:362–7.PubMedCrossRef Franke FE, Steger K, Marks A, Kutzner H, Mentzel T. Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas. J Cutan Pathol. 2004;31:362–7.PubMedCrossRef
6.
go back to reference Kahn HJ, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest. 2002;82:1255–7.PubMed Kahn HJ, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest. 2002;82:1255–7.PubMed
7.
go back to reference Nisato RE, Tille JC, Pepper MS. Lymphangiogenesis and tumor metastasis. Thromb Haemost. 2003;90:591–7.PubMed Nisato RE, Tille JC, Pepper MS. Lymphangiogenesis and tumor metastasis. Thromb Haemost. 2003;90:591–7.PubMed
8.
go back to reference Müller AM, Franke FE, Müller KM. D2-40: a reliable marker in the diagnosis of pleural mesothelioma. Pathobiology. 2006;73:50–4.PubMedCrossRef Müller AM, Franke FE, Müller KM. D2-40: a reliable marker in the diagnosis of pleural mesothelioma. Pathobiology. 2006;73:50–4.PubMedCrossRef
9.
go back to reference Renyi-Vamos F, Tovari J, Fillinger J, et al. Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res. 2005;11:7344–53.PubMedCrossRef Renyi-Vamos F, Tovari J, Fillinger J, et al. Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res. 2005;11:7344–53.PubMedCrossRef
10.
go back to reference Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non–small cell lung cancer. Oncol Rep. 2006;15:437–42.PubMed Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non–small cell lung cancer. Oncol Rep. 2006;15:437–42.PubMed
11.
go back to reference Okudera K, Kamata Y, Takanashi S, et al. Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis. Pathol Int. 2006;56:494–502.PubMedCrossRef Okudera K, Kamata Y, Takanashi S, et al. Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis. Pathol Int. 2006;56:494–502.PubMedCrossRef
12.
go back to reference Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. Histological typing of lung and pleural tumors. In: Travis WD, editor. World Health Organization international histological classification of tumors. 3rd ed. Berlin: Springer, 1999:21–66. Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. Histological typing of lung and pleural tumors. In: Travis WD, editor. World Health Organization international histological classification of tumors. 3rd ed. Berlin: Springer, 1999:21–66.
13.
go back to reference Vermeulen PB, Gasparini G, Fox SB, et al. Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer. 1996;32:2474–84.CrossRef Vermeulen PB, Gasparini G, Fox SB, et al. Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer. 1996;32:2474–84.CrossRef
14.
go back to reference Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer. 2007;110:1287–94.PubMedCrossRef Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer. 2007;110:1287–94.PubMedCrossRef
15.
go back to reference Saad RS, Kordunsky L, Liu YL, et al. Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol. 2006;19:1317–23.PubMedCrossRef Saad RS, Kordunsky L, Liu YL, et al. Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol. 2006;19:1317–23.PubMedCrossRef
16.
go back to reference Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol. 2006;37:1193–9.PubMedCrossRef Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol. 2006;37:1193–9.PubMedCrossRef
17.
go back to reference Mori D, Yamasaki F, Shibaki M, Tokunaga O. Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma. Mod Pathol. 2007;20:694–700.PubMedCrossRef Mori D, Yamasaki F, Shibaki M, Tokunaga O. Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma. Mod Pathol. 2007;20:694–700.PubMedCrossRef
18.
go back to reference Gombos Z, Xu X, Chu CS, Zhang PJ, Acs G. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res. 2005;11:8364–71.PubMedCrossRef Gombos Z, Xu X, Chu CS, Zhang PJ, Acs G. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res. 2005;11:8364–71.PubMedCrossRef
19.
go back to reference Fogt F, Zimmerman RL, Ross HM, Daly T, Gausas RE. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep. 2004;11:47–50.PubMed Fogt F, Zimmerman RL, Ross HM, Daly T, Gausas RE. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep. 2004;11:47–50.PubMed
20.
go back to reference Saad RS, Lindner JL, Lin X, Liu YL, Silverman JF. The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement. Diagn Cytopathol. 2006;34:801–6.PubMedCrossRef Saad RS, Lindner JL, Lin X, Liu YL, Silverman JF. The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement. Diagn Cytopathol. 2006;34:801–6.PubMedCrossRef
21.
go back to reference Adachi Y, Nakamura H, Kitamura Y, et al. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int. 2007;57:171–7.PubMedCrossRef Adachi Y, Nakamura H, Kitamura Y, et al. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int. 2007;57:171–7.PubMedCrossRef
22.
go back to reference Ordóñez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol. 2005;36:372–80.PubMedCrossRef Ordóñez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol. 2005;36:372–80.PubMedCrossRef
23.
go back to reference Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science. 2002;296:1883–6.PubMedCrossRef Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science. 2002;296:1883–6.PubMedCrossRef
24.
go back to reference Arnaout-Alkarain A, Kahn HJ, Narod SA, Sun PA, Marks AN. Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer. Mod Pathol. 2007;20:183–91.PubMedCrossRef Arnaout-Alkarain A, Kahn HJ, Narod SA, Sun PA, Marks AN. Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer. Mod Pathol. 2007;20:183–91.PubMedCrossRef
25.
go back to reference Van den Eynden GG, Van der Auwera I, Van Laere SJ, et al. Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study. Br J Cancer. 2006;94:1643–9.PubMed Van den Eynden GG, Van der Auwera I, Van Laere SJ, et al. Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study. Br J Cancer. 2006;94:1643–9.PubMed
26.
go back to reference Shields JD, Borsetti M, Rigby H, et al. Lymphatic density and metastatic spread in human malignant melanoma. Br J Cancer. 2004;90:693–700.PubMedCrossRef Shields JD, Borsetti M, Rigby H, et al. Lymphatic density and metastatic spread in human malignant melanoma. Br J Cancer. 2004;90:693–700.PubMedCrossRef
Metadata
Title
D2-40-Positive Lymphatic Vessel Density Is a Poor Prognostic Factor in Squamous Cell Carcinoma of the Lung
Authors
Shotaro Iwakiri, MD
Shinjiro Nagai, PhD, MD
Hiromichi Katakura, PhD, MD
Kazumasa Takenaka, PhD, MD
Hiroshi Date, PhD, MD
Hiromi Wada, PhD, MD
Fumihiro Tanaka, PhD, MD
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0432-6

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