Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma.
BACKGROUND
Neovascularization was shown to be critically involved in the progression of multiple cancers, and treatment approaches targeting tumor-associated neovascularization provide convincing results in recent years in some tumor entities. However, little is known about the tumor-associated neovascularization in hilar cholangiocarcinoma. The present study was conducted to analyze tumor-associated neovascularization in hilar cholangiocarcinoma and to determine its influence on tumor growth, metastasis, recurrence, and prognosis.


METHODS
We analyzed tissue specimens of hilar cholangiocarcinoma (n = 60) by immunohistochemistry using the endothelial-specific antibody CD31 and subsequently quantified the microvessel density (MVD). The MVD was correlated with clinicopathological characteristics and recurrence pattern of the tumors as well as survival of patients.


RESULTS
Hilar cholangiocarcinoma revealed a high degree of vascularization, with a calculated mean MVD of 28.1 +/- 14.5 vessels. Tumors with a high MVD had a significant higher incidence of lymph node involvement (P = 0.009) and local recurrence (P < 0.001). Furthermore, a high MVD was identified to be a significant overall survival disadvantage (3-year, 28% vs. 93%; 5-year, 8% vs. 78%; P < 0.001) as well as disease-free survival disadvantage (3-year, 7% vs. 88%, 5-year, 7% vs. 72%; P < 0.001), with MVD representing an independent prognostic factor for survival.


CONCLUSIONS
Neovascularization is associated with nodal spread as well as local recurrence and serves as an independent prognostic factor for survival after curative resection of hilar cholangiocarcinoma. Therefore, tumor-associated neovascularization seems to be critically involved in the progression of this tumor entity. In addition, neovascularization may represent a potential target in he development of new therapeutic approaches in hilar cholangiocarcinoma.
Thelen
Armin
A
Department of General, Visceral and Transplantation Surgery, Charité Universitaetsmedizin Berlin, Berlin, Germany.
Scholz
Arne
A
Benckert
Christoph
C
Schröder
Maik
M
Weichert
Wilko
W
Wiedenmann
Bertram
B
Neuhaus
Peter
P
Jonas
Sven
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D011379:Prognosis; D015996:Survival Rate
D019408:Platelet Endothelial Cell Adhesion Molecule-1