Taylor Matthew D, Smith Philip W, Brix William K, Wick Mark R, Theodosakis Nicholas, Swenson Brian R, Kozower Benjamin D, Jones David R
Department of Surgery, University of Virginia, Charlottesville, VA, USA.
Eur J Cardiothorac Surg. 2009 Apr;35(4):699-705. doi: 10.1016/j.ejcts.2008.11.029. Epub 2009 Jan 10.
Esophageal cancer tumor biology is best assessed clinically by 2-[18F]fluoro-2-deoxy-d-glucose (FDG)-PET. Both FDG-PET maximal positron emission tomography (PET) standardized uptake values (SUVmax) and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in esophageal cancer. Interestingly, there is limited data examining the relationship between FDG-PET SUVmax and expression of these tumor markers in esophageal cancer. The purpose of this study was to determine the correlation of tumor markers with FDG-PET SUVmax in esophageal cancer.
FDG-PET SUVmax was calculated in 67 patients with esophageal cancer of which 59 (88%) had adenocarcinoma. Neoadjuvant radiotherapy and/or chemotherapy were administered to 42% (28/67) of patients. Esophageal tumor tissue and surrounding normal tissue was obtained and tissue microarrays were created. Immunohistochemical analysis was performed for five known esophageal cancer tumor markers (GLUT-1, p53, cyclin D1, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF)). Assessment of each tumor marker was made by two independent, blinded pathologists using common grading criteria of intensity and percentage of cells stained. A p value <0.05 was considered significant.
There were 55 men (82%) and 12 women (18%) with a median age of 63 years (range 40-83). Pathologic staging included stage I (n=29, 43%), stage II (n=19, 28%), stage III disease (n=18, 27%), and stage IV disease (n=1, 2%). PET SUVmax correlated with T stage (p=0.001). In patients undergoing surgery without induction therapy, increasing SUVmax values correlated with increased expression of GLUT-1 transporter (p=0.01). There was no correlation between SUVmax and EGFR, cyclin D1, VEGF, or p53 expression in primary tumor.
FDG-PET SUVmax correlates with an increased expression of GLUT-1 transporter in esophageal cancer specimens not subjected to induction therapy. No significant difference in tumor marker expression was noted between patients undergoing induction therapy or surgery alone except p53 expression decreased in primary tumors following induction therapy. Failure of SUVmax values to correlate with known prognostic esophageal cancer tumor markers suggests that FDG-PET may have limited clinical utility in assessing response to therapies targeting these markers.
食管癌肿瘤生物学特性最好通过2-[18F]氟-2-脱氧-D-葡萄糖(FDG)-PET进行临床评估。FDG-PET最大正电子发射断层扫描(PET)标准化摄取值(SUVmax)以及选定的肿瘤标志物均已显示与食管癌的分期、淋巴结疾病及生存率相关。有趣的是,关于FDG-PET SUVmax与食管癌中这些肿瘤标志物表达之间关系的数据有限。本研究的目的是确定食管癌中肿瘤标志物与FDG-PET SUVmax的相关性。
计算了67例食管癌患者的FDG-PET SUVmax,其中59例(88%)为腺癌。42%(28/67)的患者接受了新辅助放疗和/或化疗。获取了食管肿瘤组织及周围正常组织,并制作了组织芯片。对五种已知的食管癌肿瘤标志物(葡萄糖转运蛋白1(GLUT-1)、p53、细胞周期蛋白D1、表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF))进行了免疫组织化学分析。由两名独立的、不知情的病理学家根据细胞染色强度和百分比的常用分级标准对每种肿瘤标志物进行评估。p值<0.05被认为具有统计学意义。
共有55名男性(82%)和12名女性(18%),中位年龄为63岁(范围40-83岁)。病理分期包括I期(n=29,43%)、II期(n=19,28%)、III期疾病(n=18,27%)和IV期疾病(n=1,2%)。PET SUVmax与T分期相关(p=0.001)。在未接受诱导治疗的手术患者中,SUVmax值升高与GLUT-1转运蛋白表达增加相关(p=0.01)。SUVmax与原发肿瘤中的EGFR、细胞周期蛋白D1、VEGF或p53表达之间无相关性。
在未接受诱导治疗的食管癌标本中,FDG-PET SUVmax与GLUT-1转运蛋白表达增加相关。在接受诱导治疗或单纯手术的患者之间,除诱导治疗后原发肿瘤中p53表达降低外,未观察到肿瘤标志物表达有显著差异。SUVmax值未能与已知的食管癌预后肿瘤标志物相关,这表明FDG-PET在评估针对这些标志物的治疗反应方面可能具有有限的临床应用价值。