Prognostic Value of Lymphangiogenesis and Lymphovascular... : Annals of Surgery (original) (raw)

Original Article

Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast Cancer

Schoppmann, Sebastian F. MD†; Bayer, Guenther MD†; Aumayr, Klaus†; Taucher, Susanne MD*; Geleff, Silvana MD†; Rudas, Margaretha MD†; Kubista, Ernst MD‡; Hausmaninger, Hubert MD§; Samonigg, Hellmut MD∥; Gnant, Michael MD*; Jakesz, Raimund MD*; Horvat, Reinhard MD† Austrian Breast and Colorectal Cancer Study Group

From the *Department of Surgery and the †Clinical Institute of Pathology, ‡Department of Special Gynecology, University of Vienna, Vienna; §Department of Internal Medicine III, Landeskrankenhaus Salzburg; and ∥Department of Medical Oncology, University of Graz, Graz, Austria. ¶The Austrian Breast and Colorectal Cancer Study Group included the following: R. Jakesz, M. Gnant, E. Kubista, M. Seifert, I. Agstner, C. Dadak, P. Dubsky, A. Galid, E. Hanzal, H. Helbich, E. Joura, D. Kandioler, K. Oberhuber, M. Ploner, G. Reiner, S. Roka, M. Pudas, C. Sam, M. Schemper, M. Schmidinger, G. Steger, B. Steiner, S. Taucher, K. Wenzl, and G. Wolf (University of Vienna); H. Hausmaninger, B. Mlineritsch, R.-C. Menzel, E. Hell, H. Kogelnik, E. Moritz, C. Papp, R. Schandalik, M. Umlauft, and H. Waclawiczek (Salzburg, Braunau, Hallein and Oberndorf Hospitals, and BHB Hospital Salzburg); H. Samonigg, H.-J. Mischinger, P. Steindorfer, E. Andritsch, H. Bacher, T. Bauernhofer, A. Berger, H. Cervenka, A. El-Shabrawi, J. Freisinger, H. Hauser, J. Hebenstreit, G. Hofmann, A.-K. Kasparek, P. Konstantiniuk, G. Kosina, P. Krippl, L. Kronberger, I. Kuss, G. Luschin-Ebengreuth, R. Moser, H. Papadi, H. Pfeifer, F. Ploner, S. Reinisch, M. Riegler, G. Rosanelli, W. Schippinger, M. Schmid, W. Schwaiger, M. Smola, H. Stöger, M. Thalhammer, I. Thiel, P. Wagner, M. Wehrschütz, R. Winter, and G. Zehetleitner (University of Graz, Graz Hospital, and BHB Hospital Graz); D. Depisch, W. Kwasny, K. Haider and T. Payrits (Wiener Neustadt Hospital); R. Kolb (Waehring Lutheran Hospital Vienna); C. Tausch, M. Aufschnaiter, D. Heck, R. Klug, F. Kugler, and R. Schildberger (BHS Hospital Linz); M. Stierer, H. Matzinger, and H. Spoula (Hanusch Hospital Vienna); K. Renner and R. Schiessel (SMZ Ost Hospital Vienna); U. Schmidbauer and M. Wunderlich (BHS Hospital Vienna); M. Fridrik and G. Wahl (Linz General Hospital); D. Bauer, F. Hofbauer, and M. Lang (Oberpullendorf Hospital); G. Jatzko and V. Wette (BHB Hospital St. Veit/Glan); J. Omann, M. Starlinger, and A. Urbania (Klagenfurt Hospital); K. Keller, W. Schennach, and H. Zoller (Zams Hospital); E. Klug, K. Mach, and K. Steflitsch (Oberwart Hospital); J. Berger, R. Lenzhofer, and G. Winter (Schwarzach Hospital); and A. Haid, R. Koeberle, and G. Zimmermann (Feldkirch Hospital).

Reprints: Sebastian F. Schoppmann, MD, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: [email protected].

Objective:

The aim of this study was to investigate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in a large cohort of breast cancer patients.

Introduction:

Invasion of tumor cells into blood and lymphatic vessels is one of the critical steps for metastasis. The presence or absence of lymph node metastasis is one of the main decision criteria for further therapy. One shortcoming of previous morphologic studies was the lack of specific markers that could exact discriminate between blood and lymphatic vessels. The aim of this study was to evaluate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in breast cancer patients.

Methods:

We investigated 374 tissue specimens of patients suffering from invasive breast cancer by immunostaining for the lymphatic endothelial specific marker podoplanin. Lymphangiogenesis, quantified by evaluating the lymphatic microvessels density (LMVD), and lymphovascular invasion (LVI) were correlated with various clinical parameters and prognostic relevance.

Results:

LMVD correlated significantly with LVI (P = 0.001). LVI was associated significantly with a higher risk for developing lymph-node metastasis (P = 0.004). Calculating the prognostic relevance, LVI presented as an independent prognostic parameter for disease free as well as overall survival (P = 0.001, and P = 0.001, respectively).

Conclusion:

Our data provide evidence that the biologic system of lymphangiogenesis constitutes a potential new target for development of anti-breast cancer therapeutic concepts. Our results further suggest that young, premenopausal patients with low differentiated breast tumors and high LMVD and LVI would, in particular, benefit from lymphangiogenesis-associated therapeutic strategies.