Hattori Seiya, Kikuchi Eiji, Kosaka Takeo, Miyazaki Yasumasa, Tanaka Nobuyuki, Miyajima Akira, Mikami Shuji, Oya Mototsugu
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Ann Surg Oncol. 2016 Feb;23(2):663-70. doi: 10.1245/s10434-015-4848-x. Epub 2015 Sep 8.
Axl, which is in the TAM family of receptor tyrosine kinases, and its ligand, growth arrest-specific gene 6 (Gas6), have been associated with worse prognoses after the surgical treatment of some types of cancers. We herein investigated the biological significance of the protein expression of Axl and Gas6 on the outcomes of patients with upper tract urothelial carcinoma (UTUC).
The protein expression of Axl and Gas6 was evaluated by immunohistochemistry, and their relationships with clinicopathological features were investigated in surgical specimens obtained from 161 patients who had been surgically treated for UTUC.
Axl labeling was strong in 67 of 161 (42 %) cases, while Gas6 labeling was strong in 72 of 161 (45 %) cases. The strong expression of Axl correlated with that of Gas6. A high pathological stage (p = 0.009), strong expression of Gas6 (p = 0.038), and strong expression of Axl (p = 0.016) were independent factors for predicting worse cancer-specific survival (CSS). In a subgroup analysis of patients with pT < 2 (N = 53), no significant difference in CSS was observed between patients weakly and strongly expressing Axl/Gas6. In contrast, a subgroup analysis of patients with pT ≥ 2 (N = 108) revealed that the expression levels of Axl and Gas6 correlated with CSS.
The protein expression of Axl and its ligand Gas6 may be a useful indicator for a worse clinical outcome in UTUC patients, especially patients with pT ≥ 2, who underwent radical nephroureterectomy.
Axl属于受体酪氨酸激酶TAM家族，其配体生长停滞特异性基因6（Gas6）与某些类型癌症手术治疗后的不良预后相关。我们在此研究了Axl和Gas6蛋白表达在上尿路尿路上皮癌（UTUC）患者预后中的生物学意义。
采用免疫组织化学法评估Axl和Gas6的蛋白表达，并在161例接受UTUC手术治疗患者的手术标本中研究它们与临床病理特征的关系。
161例中有67例（42%）Axl标记强阳性，161例中有72例（45%）Gas6标记强阳性。Axl的强表达与Gas6的强表达相关。高病理分期（p = 0.009）、Gas6强表达（p = 0.038）和Axl强表达（p = 0.016）是预测癌症特异性生存（CSS）较差的独立因素。在pT < 2（N = 53）患者的亚组分析中，Axl/Gas6弱表达和强表达患者之间的CSS无显著差异。相反，pT≥2（N = 108）患者的亚组分析显示，Axl和Gas6的表达水平与CSS相关。
Axl及其配体Gas6的蛋白表达可能是UTUC患者，尤其是接受根治性肾输尿管切除术的pT≥2患者临床预后较差的有用指标。
