The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma.
OBJECTIVE
Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC).


METHODS
We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes.


RESULTS
Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer-specific survival rates were 66.1% and 72.8% in patients with VASH1 density (≥ 40/mm(2)) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer-specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion.


CONCLUSIONS
VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC.
Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yasumasa
Y
Miyazaki
Takeo
T
Kosaka
Shuji
S
Mikami
Eiji
E
Kikuchi
Nobuyuki
N
Tanaka
Takahiro
T
Maeda
Masaru
M
Ishida
Akira
A
Miyajima
Ken
K
Nakagawa
Yasunori
Y
Okada
Yasufumi
Y
Sato
Mototsugu
M
Oya
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014571:Urologic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C493181:VASH1 protein, human