Kinouchi Toshiaki, Mano Masayuki, Matsuoka Ikuyo, Kodama Sae, Aoki Tomomi, Okamoto Mina, Yamamura Hisako, Usami Michiyuki, Takahashi Katsuhito
Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
Urology. 2003 Oct;62(4):765-70. doi: 10.1016/s0090-4295(03)00512-0.
To investigate the correlation between pathologic findings and maturation of the tumor neovasculature of renal cell carcinoma by immunohistochemical studies.
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).
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.
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.
通过免疫组织化学研究探讨肾细胞癌病理结果与肿瘤新生血管成熟度之间的相关性。
采用间接免疫过氧化物酶法，用小鼠单克隆抗体抗人CD31、抗α平滑肌肌动蛋白（αSMA）和抗人钙调蛋白对25例随机选取的肾细胞癌患者的福尔马林固定石蜡包埋标本进行染色。在每个患者微血管数量较多的六个区域，于200倍放大倍数下（每个区域0.255平方毫米）计数微血管。
3级肿瘤中CD31阳性微血管数量显著低于1级或2级肿瘤（分别为P = 0.003222和P = 0.043217）。高分期、肿瘤大小大于4.5厘米或非透明细胞型的肿瘤，其CD31阳性微血管计数显著低于低分期、大小小于4.6厘米或透明细胞型的肿瘤。在3级肿瘤中，αSMA阳性微血管数量与CD31阳性微血管数量的表达比值与1级或2级肿瘤相比显著降低（分别为P = 0.000011和P = 0.000000）。未观察到肿瘤新生血管中钙调蛋白的表达。高分期、较大肿瘤大小或非透明细胞型中，αSMA阳性微血管数量与CD31阳性微血管数量的表达比值显著降低。
高分级和高分期肿瘤的肿瘤新生血管不成熟。这些结果表明，肾细胞癌的高分级肿瘤可能对诱导不成熟肿瘤血管凋亡的抗血管生成治疗敏感。
