Immature tumor angiogenesis in high-grade and high-stage renal cell carcinoma.
OBJECTIVE
To investigate the correlation between pathologic findings and maturation of the tumor neovasculature of renal cell carcinoma by immunohistochemical studies.


METHODS
Formalin-fixed and paraffin-embedded specimens from 25 randomly selected patients with renal cell carcinoma were stained with mouse monoclonal antibodies, anti-human CD31, anti-alpha smooth muscle actin (alphaSMA), and anti-human calponin by the indirect immunoperoxidase method. The microvessels were counted in six areas with the higher number of microvessels in each patient at 200x magnification (0.255 mm2 per area).


RESULTS
The number of CD31-positive microvessels in grade 3 tumors was significantly lower than those in grade 1 or 2 tumors (P = 0.003222 and P = 0.043217, respectively). The CD31-positive microvessel counts of those of higher stage, tumor size greater than 4.5 cm, or non-clear cell type were significantly lower than tumors of lower stage, size less than 4.6 cm, or clear cell type. In the grade 3 tumors, the expression ratio of the number of alphaSMA-positive microvessels to the number of CD31-positive microvessels was significantly decreased compared with grade 1 or 2 tumors (P = 0.000011 and P = 0.000000, respectively). The expression of calponin in the tumor neovasculature was not observed. The expression ratios of the number of alphaSMA-positive microvessels to the number of CD31-positive microvessels in higher stages, larger tumor sizes, or non-clear cell types were significantly decreased.


CONCLUSIONS
The tumor neovasculature of high-grade and high-stage tumors was immature. These results imply that high-grade tumors of renal cell carcinomas may be susceptible to antiangiogenesis therapy inducing apoptosis of immature tumor vessels.
Kinouchi
Toshiaki
T
Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
Mano
Masayuki
M
Matsuoka
Ikuyo
I
Kodama
Sae
S
Aoki
Tomomi
T
Okamoto
Mina
M
Yamamura
Hisako
H
Usami
Michiyuki
M
Takahashi
Katsuhito
K
D000199:Actins / Q000032:analysis; D018262:Adenocarcinoma, Clear Cell / Q000098:blood supply / Q000473:pathology; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002135:Calcium-Binding Proteins / Q000032:analysis; D002196:Capillaries / Q000737:chemistry / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D000096985:Calponins
D000199:Actins; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000096985:Calponins