Mizuno Tomoya, Kamai Takao, Abe Hideyuki, Sakamoto Setsu, Kitajima Kazuhiro, Nishihara Daisaku, Yuki Hideo, Kambara Tsunehito, Betsunoh Hironori, Yashi Masahiro, Fukabori Yoshitatsu, Kaji Yasushi, Yoshida Ken-Ichiro
Department of Urology, Dokkyo Medical University, 880 Kitakobayashi Mibu, Tochigi, 321-0293, Japan,
BMC Cancer. 2015;15:1097. doi: 10.1186/s12885-015-1097-0. Epub 2015 Mar 10.
The relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3'kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view.
Seventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features.
The average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients.
A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.
正电子发射断层扫描（PET）联合[18F]氟脱氧葡萄糖（18F-FDG PET）测定的标准化摄取值（SUV）与人类肾细胞癌（RCC）临床病理特征及分子改变之间的关系尚未阐明。另一方面，在包括RCC在内的多种人类癌症中均检测到磷脂酰肌醇3'激酶（PI3K）、丝氨酸/苏氨酸激酶Akt和雷帕霉素靶蛋白（mTOR）通路的过度激活。到目前为止，关于人类RCC中SUV与这些蛋白之间的关系知之甚少。因此，从分子角度研究SUV与人类RCC临床病理特征的相关性具有重要意义。
分析77例接受肾切除术并在术前通过18F-FDG PET测定最大SUV（SUVmax）的连续性RCC患者。我们研究了原发肿瘤中SUVmax、磷酸化Akt（Ser-473）（pAkt(Ser-473)）、磷酸化Akt（Thr-308）（pAkt(Thr-308)）和磷酸化S6核糖体蛋白（Ser-235/236）（pS6）蛋白水平与各种临床病理特征之间的关系。
原发肿瘤的平均SUVmax为6.9（1.5至40.3）。较高的SUVmax与原发肿瘤中pAkt(Ser-473)、pAkt(Thr-308)和pS6蛋白的高表达相关。原发肿瘤较高的SUVmax以及pAkt(Ser-473)、pAkt(Thr-308)和pS6表达增加与肿瘤分化较差、较高的pT分期、区域淋巴结受累、微血管侵犯和远处转移相关，也与局限性或局部进展性且无远处转移（cTanyNanyM0）的患者根治性肾切除术后早期复发以及所有患者较短的总生存期相关。
18F-FDG PET上较高的SUVmax与RCC肿瘤中pAkt和pS6蛋白水平升高、侵袭性行为和转移潜能相关，也与根治性肾切除术后早期复发和较短的总生存期相关。这些发现表明SUVmax可能有助于预测RCC的生物学特征。
