Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma.
BACKGROUND
The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC).


METHODS
Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled-stained for a pericyte marker (alpha smooth muscle actin [α-SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels. The correlations of PC and the MVD:PC ratio with clinicopathologic characteristics were analyzed.


RESULTS
There was an inverse correlation between differentiated MVD and PC. Higher PC correlated with more aggressive clinicopathologic characteristics of CCRCC in both cohorts, including more advanced T-classification, higher pathologic grades, and the occurrence of tumor necrosis. The MVD:PC ratio was an independent favorable prognostic factor for overall and recurrence-free survival in the Asian cohort and for recurrence-free survival in the US cohort. PC also was an independent prognostic factor, with higher PC predicting a poorer outcome. The combination of PC and MVD was better at distinguishing the outcome of patients with CCRCC. PC combined with differentiated MVD or with the MVD:PC ratio provided additional, independent prognostic information to the Leibovich risk model, and that information was used to generate improved risk models.


CONCLUSIONS
The authors consistently observed that higher PC was correlated with more aggressive clinicopathologic characteristics. PC was an independent unfavorable prognostic factor. The authors concluded that pericytes should be considered for therapeutic targeting.
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong, China.
Yun
Y
Cao
Zhi-Ling
ZL
Zhang
Ming
M
Zhou
Paul
P
Elson
Brian
B
Rini
Hakan
H
Aydin
Kristin
K
Feenstra
Min-Han
MH
Tan
Bree
B
Berghuis
Rebeka
R
Tabbey
James H
JH
Resau
Fang-Jian
FJ
Zhou
Bin Tean
BT
Teh
Chao-Nan
CN
Qian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020286:Pericytes / Q000473:pathology*; D011379:Prognosis; D012306:Risk; D018709:Statistics, Nonparametric; D055815:Young Adult