Correlation between S100 family proteins and renal cell carcinoma - Possibility of early diagnosis and molecular targeting therapy

本研究旨在探讨S100 A10、annexin II和B-FABP基因在肾细胞癌中的表达及其作为肿瘤标志物的潜在价值。此外，分析基因表达与肾癌预后指标之间的任何相关性。通过RT-PCR评估手术切除的肾脏样品的非肿瘤（正常）和肿瘤部分（n=47）中每个基因的表达。每种抗原在RCC和正常肾组织（n=13）中免疫染色。S100 A10在正常组织和肿瘤组织中的表达分别为0.38±0.06和0.95±0.14（p<0.0001，t检验）。相似地，膜联蛋白II的表达为0.73±0.05和1.20±0.12（p<0.0003）。在RCC的所有组织切片中，S100 A10和膜联蛋白II被膜免疫染色。在正常肾上皮中，两种抗原均在Bowman囊和Henle袢通过集合管系统的小管中染色，但在大多数RCC来源的近端小管中不染色。另一方面，B-FABP的表达分别为0.04±0.02和0.78±0.14（p<0.0001），47个癌样品中有36个过表达B-FABP（p<0.005，□2检验）。在正常肾组织切片中未检测到B-FABP，但在超过三分之二的RCC组织切片中有细胞质染色。在核级G1样品中，膜联蛋白II与S100 A10共过表达（7/8，p<0.05）。另一方面，S100 A10和B-FABP的过表达与分级和分期无关。3个基因均可作为肾细胞癌的标志物，其中B-FABP基因对肾细胞癌的特异性最强。S100 A10和annexin II的共同过表达与肾癌预后良好的指标明显相关。

The present study was conducted to analyze the expression of S100A10, annexin II and B-FABP genes in renal cell carcinoma (RCC) and their potential value as the tumor marker. Furthermore, any correlation between the gene expression and prognostic indicators of RCC was analyzed. Expression of each gene was estimated by RT-PCR in the non-neoplastic (normal) and tumor parts of surgically resected kidney samples (n=47). Each antigen was immunostained in RCC and normal kidney tissues (n=13). Expression of S100A10 in the normal and tumor parts was in average 0.38±0.06 and 0.95±0.14, respectively, (p<0.0001, t-test) after the standarization against that of □-actin. Similarly, expression of annexin II was 0.73±0.05 and 1.20±0.12 (p<0.0003). In all tissue sections of RCC,S100A10 and annexin II were membraneously immunostained. In the normal renal epithelia, however, both antigens were stained in the Bowman's capsule and the tubules from Henle's loop through collecting duct system but not in the proximal tubules, from where most RCCs are derived. On the other hand, expression of B-FABP was 0.04±0.02 and 0.78±0.14 (p<0.0001), respectively, and 36 of 47 carcinoma samples overexpressed B-FABP (p<0.005,□2-test). No B-FABP was immunohistochemically detected in normal kidney sections, but it was cytoplasmically stained in more than two-third of RCC tissue sections. In nuclear grade G1 samples, annexin II was co-overexpressed with S100A10 (7/8,p<0.05). On the other hand, S100A10 and B-FABP was overexpressed regardless of the grade and stage. The three genes were good as RCC markers, and B-FABP was most specific to RCC. Co-overexpression of S100A10 and annexin II was apparently correlated with an indicator for favorable prognosis of RCC.