Daniel L, Lechevallier E, Giorgi R, Sichez H, Zattara-Cannoni H, Figarella-Branger D, Coulange C
Department of Pathology, CHU Timone, Marseille, France.
Hum Pathol. 2001 Mar;32(3):282-7. doi: 10.1053/hupa.2001.22753.
To assess the expression of the homeogene Pax-2 in adult renal cell carcinomas, we did a retrospective immunohistochemical analysis of 56 frozen tumor samples representing all major histologic subtypes of renal tumors. There were 33 conventional renal cell carcinomas (58.9%), 12 papillary renal cell carcinomas (21.4%), 4 chromophobe cell renal carcinomas, 4 urothelial cell renal carcinomas, and 3 oncocytomas. Forty-five tumors (62.5%) were localized, and 21 tumors had extrarenal involvement. Eight patients (14%) had metastatic disease at the end of the follow-up. We searched for relationships between Pax-2 expression and nuclear grading, TNM staging, Ki-67 proliferation index, expression of transforming growth factor-beta1 (TGF-beta 1), an in vitro down-regulator of Pax-2 expression, and finally cytogenetic abnormalities. All histologic subtypes expressed Pax-2 protein, except urothelial renal carcinomas. The highest expression was in papillary renal cell carcinomas. In this subtype, all tumors and 83.3% +/- 12.3% of tumor cells were immunoreactive for Pax-2. All but 2 conventional renal cell carcinomas expressed Pax-2, but with 26.3% +/- 29.6% of immunoreactive cells (P <.001). Pax-2 expression was not correlated with nuclear grading (P =.6), tumor size (P =.3), and TGF-beta 1 expression (P =.1). Nevertheless, Pax-2 expression correlated with the Ki-67 proliferation index only for the conventional histologic subtype (P =.03). In this histologic subtype, Pax-2 expression was higher in patients with metastatic disease than in those without (P =.02). Pax-2 expression was not associated with specific cytogenetic abnormalities like trisomy 7 (P =.1), 3p deletion (P =.5), and hyperdiploidy (P =.2). TGF-beta 1 expression, positive in 33 tumors (59%), was not correlated with either Pax-2 expression (P =.1) or current prognostic factors such as nuclear grading (P =.2). Interestingly, we also observed an expression of TGF-beta RI and TGF-beta RII in the tumors with high nuclear grading (P =.005). We conclude that Pax-2 protein is expressed in all major histologic subtypes of renal cell carcinomas. The pattern of expression differs between these subtypes. Pax-2 expression in conventional renal cell carcinomas is correlated with the proliferation index and is significantly higher in patients with metastatic disease. HUM PATHOL 32:282-287.
为评估同源基因Pax-2在成人肾细胞癌中的表达情况，我们对56份冷冻肿瘤样本进行了回顾性免疫组化分析，这些样本代表了肾肿瘤的所有主要组织学亚型。其中有33例传统型肾细胞癌（58.9%）、12例乳头状肾细胞癌（21.4%）、4例嫌色细胞肾细胞癌、4例尿路上皮细胞肾细胞癌和3例嗜酸细胞瘤。45例肿瘤（62.5%）局限于肾内，21例肿瘤有肾外侵犯。8例患者（14%）在随访结束时出现转移。我们探寻了Pax-2表达与核分级、TNM分期、Ki-67增殖指数、转化生长因子-β1（TGF-β1，一种Pax-2表达的体外下调因子）的表达以及最终细胞遗传学异常之间的关系。除尿路上皮肾细胞癌外，所有组织学亚型均表达Pax-2蛋白。最高表达见于乳头状肾细胞癌。在该亚型中，所有肿瘤及83.3%±12.3%的肿瘤细胞对Pax-2呈免疫反应性。除2例传统型肾细胞癌外，其余均表达Pax-2，但免疫反应性细胞占26.3%±29.6%（P<0.001）。Pax-2表达与核分级（P=0.6）、肿瘤大小（P=0.3）及TGF-β1表达（P=0.1）均无相关性。然而，仅在传统组织学亚型中，Pax-2表达与Ki-67增殖指数相关（P=0.03）。在该组织学亚型中，有转移的患者Pax-2表达高于无转移者（P=0.02）。Pax-2表达与7号染色体三体（P=0.1）、3p缺失（P=0.5）及超二倍体（P=0.2）等特定细胞遗传学异常无关。33例肿瘤（59%）中TGF-β1表达阳性，其与Pax-2表达（P=0.1）或核分级等当前预后因素（P=0.2）均无相关性。有趣的是，我们还观察到在高核分级肿瘤中TGF-βRI和TGF-βRII的表达（P=0.005）。我们得出结论，Pax-2蛋白在肾细胞癌的所有主要组织学亚型中均有表达。这些亚型之间的表达模式不同。传统型肾细胞癌中Pax-2表达与增殖指数相关，且在有转移的患者中显著更高。《人类病理学》32:282 - 287。
