Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 313-334 |
| Number of pages | 22 |
| Journal | Cancer |
| Volume | 119 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2013 |
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Keywords
- clear cell renal cell carcinoma
- microvessel density
- pericyte
- prognosis, survival
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma. / Cao, Yun; Zhang, Zhi Ling; Zhou, Ming; Elson, Paul; Rini, Brian; Aydin, Hakan; Feenstra, Kristin; Tan, Min Han; Berghuis, Bree; Tabbey, Rebeka; Resau, James H.; Zhou, Fang Jian; Teh, Bin Tean; Qian, Chao Nan.
In: Cancer, Vol. 119, No. 2, 15.01.2013, p. 313-334.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma
AU - Cao, Yun
AU - Zhang, Zhi Ling
AU - Zhou, Ming
AU - Elson, Paul
AU - Rini, Brian
AU - Aydin, Hakan
AU - Feenstra, Kristin
AU - Tan, Min Han
AU - Berghuis, Bree
AU - Tabbey, Rebeka
AU - Resau, James H.
AU - Zhou, Fang Jian
AU - Teh, Bin Tean
AU - Qian, Chao Nan
PY - 2013/1/15
Y1 - 2013/1/15
N2 - 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.
AB - 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.
KW - clear cell renal cell carcinoma
KW - microvessel density
KW - pericyte
KW - prognosis, survival
UR - http://www.scopus.com/inward/record.url?scp=84872088791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872088791&partnerID=8YFLogxK
U2 - 10.1002/cncr.27746
DO - 10.1002/cncr.27746
M3 - Article
C2 - 22811049
AN - SCOPUS:84872088791
VL - 119
SP - 313
EP - 334
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 2
ER -