Cascinu S, Graziano F, Valentini M, Catalano V, Giordani P, Staccioli M P, Rossi C, Baldelli A M, Grianti C, Muretto P, Catalano G
Medical Oncology, Hospital of Parma, Italy.
Ann Oncol. 2001 Feb;12(2):239-44. doi: 10.1023/a:1008339408300.
The behaviour of colorectal carcinomas may depend on molecular properties of tumors. In node-positive colon cancer, we assessed the S-phase fraction (SPF) index, the vascular endothelial growth factor (VEGF) expression and the TS levels. The combined analysis of SPF/VEGF was studied for predictivity of recurrent disease, the TS quantitation was related to the efficacy of fluorouracil-based adjuvant chemotherapy.
Consecutive patients with surgically-resected, node-positive colon cancer were studied. Flow cytometry for the SPF and immunohistochemistries for the TS and the VEGF expression were carried out on the primary tumor. Recurrences had to be proven by biopsy or surgery, and they were categorized as early, if occurred within 12 months after surgery, or late if occured 13 months or more.
Of 150 evaluable patients, 100 had received fluorouracil-based adjuvant chemotherapy and 50 control patients were untreated. The combined analysis of the VEGF and the SPF showed a strong association between the two markers; 48 patients (32%) had high SPF/VEGF positive tumors and 69 patients (46%) had low SPF/VEGF negative tumors (P < 0.0001). The majority of disease-free patients (73.4%) showed VEGF negative/low SPF tumors (P < 0.0001). Early recurrences occurred more frequently in patients with VEGF positive/high SPF tumors (P < 0.001). In the 100 patients treated with adjuvant chemotherapy, 86% of relapsed patients had TS overexpressing tumors and 69% of disease-free patients had TS negative tumors (P < 0.001). Also, early recurrences occurred more frequently in TS overexpressing tumors (P < 0.0001).
Evidence is supported that node-positive colon cancer constitutes a heterogenous disease. Patients with VEGF positive/high SPF tumors showed an unfavourable outcome compared to patients with VEGF negative/low SPF tumors. The efficacy of fluorouracil-based adjuvant chemotherapy may depend on the TS status.
结直肠癌的行为可能取决于肿瘤的分子特性。在淋巴结阳性结肠癌中，我们评估了S期分数（SPF）指数、血管内皮生长因子（VEGF）表达和胸苷酸合成酶（TS）水平。研究了SPF/VEGF的联合分析对复发疾病的预测性，TS定量与基于氟尿嘧啶的辅助化疗疗效相关。
对连续的手术切除的淋巴结阳性结肠癌患者进行研究。对原发性肿瘤进行SPF的流式细胞术检测以及TS和VEGF表达的免疫组织化学检测。复发必须通过活检或手术证实，若在术后12个月内发生则分类为早期复发，若在13个月或更长时间发生则为晚期复发。
在150例可评估患者中，100例接受了基于氟尿嘧啶的辅助化疗，50例对照患者未接受治疗。VEGF和SPF的联合分析显示这两个标志物之间存在强关联；48例患者（32%）有高SPF/VEGF阳性肿瘤，69例患者（46%）有低SPF/VEGF阴性肿瘤（P < 0.0001）。大多数无病患者（73.4%）表现为VEGF阴性/低SPF肿瘤（P < 0.0001）。VEGF阳性/高SPF肿瘤患者早期复发更频繁（P < 0.001）。在接受辅助化疗的100例患者中，86%的复发患者有TS过表达肿瘤，69%的无病患者有TS阴性肿瘤（P < 0.001）。此外，TS过表达肿瘤患者早期复发更频繁（P < 0.0001）。
有证据支持淋巴结阳性结肠癌是一种异质性疾病。与VEGF阴性/低SPF肿瘤患者相比，VEGF阳性/高SPF肿瘤患者的预后不佳。基于氟尿嘧啶的辅助化疗疗效可能取决于TS状态。
