Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma

Imao, Tetsuya; Egawa, Masayuki; Takashima, Hiroshi; Kawakami, Kiyoshi; Namiki, Mikio

doi:10.1111/j.1442-2042.2004.00931.x

Cited by 57 publications

(56 citation statements)

References 31 publications

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“…As summarized in Table 1, higher MVD has been reported in many studies to be a favorable prognostic factor (eg, a higher blood vessel density in CCRCC is correlated with a better prognosis or longer patient survival). 4,[14][15][16][17][18][19][20][21][22] However, other studies have reported opposite results correlating higher MVD with poorer prognosis, [23][24][25][26][27][28] whereas others have been unable to find a significant prognostic role for MVD. [29][30][31][32][33] The controversy could result from many nonmechanistic factors, including sample size, sampling bias, the different blood vessel markers chosen for immunohistochemical (IHC) characterization, the quality of IHC staining, the methods of vasculature quantification, and the methods of interpretation.…”

Section: Differential Analysis Of Tumor Vasculaturementioning

confidence: 56%

Complexity of tumor vasculature in clear cell renal cell carcinoma

Qian

Huang

Wondergem

et al. 2009

Cancer

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Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC-namely, undifferentiated and differentiated-correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. Clear cell renal cell carcinoma (CCRCC) is a highly vascularized malignancy. As evaluated by 2-phase multidetector computed tomography angiography, CCRCC is found to be able to develop an aberrant capsular vascular supply with outflow through an ovarian vein or testicular vein, 1 although positron emission tomography shows that blood perfusion of the tumor is reduced compared with normal kidney tissues. 2 Our expression profiling study also indicated that the expression level of vascular endothelial growth factor (VEGF; a potent proangiogenesis factor) in CCRCC is 5-fold higher than in other types of kidney

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Section: Differential Analysis Of Tumor Vasculaturementioning

confidence: 56%

Complexity of tumor vasculature in clear cell renal cell carcinoma

Qian

Huang

Wondergem

et al. 2009

Cancer

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“…An interesting observation is that Lim1 silencing in tumors of human CCC-bearing nude mice did not affect tumor vascularization. It should be noted, however, that reports dealing with the prognostic value of vascularisation in human CCC have shown either no effect on patient survival, better survival, or worse prognosis (MacLennan and Bostwick, 1995;Nativ et al, 1998;Imao et al, 2004;Yao et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma

et al. 2010

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“…RCC is a hypervascular tumour for which data on the relationship between tumour vascularity and prognosis are conflicting [1]. Yoshino et al [2] and Paradis et al [3] reported that patient survival was significantly correlated with microvessel density (MVD), while others [4][5][6] reported that MVD did not correlate with metastasis.…”

Section: Introductionmentioning

confidence: 99%

Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma

et al. 2007

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OBJECTIVE To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer‐specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC). PATIENTS AND METHODS Vessels were labelled in sections of formalin‐fixed, paraffin‐embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high‐power fields (HPF, ×400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS. RESULTS In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low‐stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high‐stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation rs = −0.68, P = 0.01, and rs = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3–4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI). CONCLUSIONS This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis.

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Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma

Cited by 57 publications

References 31 publications

Complexity of tumor vasculature in clear cell renal cell carcinoma

Complexity of tumor vasculature in clear cell renal cell carcinoma

LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma

Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma

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