Two distinct types of blood vessels in clear cell renal cell carcinoma have contrasting prognostic implications.
OBJECTIVE
Intratumoral microvascular density (MVD) has been controversial as an indicator of prognosis in clear cell renal cell carcinoma (CCRCC). Classification of the intratumoral blood vessels based on differential expressions of blood vessel markers has not been correlated with patient prognosis in CCRCC. In this study, we aimed to evaluate the association of different categories of blood vessels with the patients' outcomes.


METHODS
Seventy-eight CCRCC patients who underwent nephrectomy alone were enrolled. Paraffin-embedded CCRCC tissues, together with 16 nonmalignant kidney cortex tissues, were used in tissue microarray analyses and conventional section analyses. The characteristics of intratumoral blood vessels were identified by multiple blood vessel markers and pericyte markers. A computerized image analysis program was used to quantitatively calculate the vascular density.


RESULTS
Two distinct types of microvessels were identified in CCRCC: undifferentiated (CD31(+)/CD34(-)) and differentiated (CD34(+)) vessels. A higher undifferentiated MVD significantly correlated with higher tumor grades and shorter patient survival. In contrast, a higher differentiated MVD significantly correlated with lower tumor grade and longer survival. Multivariate analyses showed that undifferentiated MVD was an independent prognostic factor for patient survival. An inverse correlation between undifferentiated MVD and differentiated MVD was also identified in CCRCC.


CONCLUSIONS
This is the first report showing distinct types of vasculature in CCRCC correlated with contrasting prognoses. A refined classification of CCRCC based on vasculature is therefore important for evaluating prognosis, and it may also have therapeutic implications.
Yao
Xin
X
Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Qian
Chao-Nan
CN
Zhang
Zhong-Fa
ZF
Tan
Min-Han
MH
Kort
Eric J
EJ
Yang
Ximing J
XJ
Resau
James H
JH
Teh
Bin Tean
BT
D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis; D001808:Blood Vessels / Q000473:pathology*; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000175:diagnosis* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011379:Prognosis; D016896:Treatment Outcome
D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1