Jeong Young-Ju, Jung Jae-Won, Cho Yoon-Young, Park Sung-Hwan, Oh Hoon-Kyu, Kang Sungmin
Department of Nuclear Medicine, Catholic University of Daegu School of Medicine.
Nucl Med Rev Cent East Eur. 2017;20(1):32-38. doi: 10.5603/NMR.a2016.0043.
Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.
Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.
pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).
pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.
肿瘤缺氧通过缺氧诱导转录因子-1α（HIF-1α）诱导多种基因的表达。它与多种癌症的预后相关。我们研究了HIF-1α在乳腺浸润性导管癌（IDC）患者中的免疫组化表达及其与原发肿瘤最大标准化摄取值（pSUVmax）以及其他生物学参数的可能相关性。还评估了pSUVmax和HIF-1α表达对预测无进展生存期（PFS）的预后意义。
纳入207例接受预处理氟-18氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（F-18 FDG PET/CT）的IDC女性患者。将pSUVmax与包括雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER2）、腋窝淋巴结（LN）转移、分期和HIF-1α表达在内的临床病理参数进行比较。使用Kaplan-Meier方法评估pSUVmax对PFS的预后价值。
与HIF-1α表达<2的患者相比，HIF-1α表达≥2的患者pSUVmax显著更高（5.2±4.5对3.7±3.1，p = 0.008）。在更高分期（p<0.000001）、ER阴性肿瘤（p<0.0001）、PR阴性肿瘤（p = 0.0011）和LN转移阳性（p = 0.0013）的患者中，pSUVmax也显著更高。与无疾病患者相比，进展患者的pSUVmax显著更高（6.8±4.4对4.1±3.7，p = 0.0005）。受试者工作特征曲线显示pSUVmax为6.51是预测PFS的最佳临界值（敏感性：53.6%，特异性：86.0%）。与低pSUVmax患者相比，高pSUVmax（>6.5）患者的PFS显著更短（p<0.0001）。
预处理F-18 FDG PET/CT上的pSUVmax反映了HIF-1α的表达，可作为预测IDC患者病情进展的良好替代标志物。FDG摄取量由乳腺癌细胞中葡萄糖代谢和缺氧的存在决定。
