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Annals of Oncology 12:239-244, 2001
© 2001 European Society for Medical Oncology

research-article

Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: Relationships with tumor recurrence and resistance to adjuvant chemotherapy

S. Cascinu1,, F. Graziano2, M. Valentini3, V. Catalano4, P. Giordani4, M. P. Staccioli5, C. Rossi5, A. M. Baldelli4, C. Grianti3, P. Muretto5 and G. Catalano4

1Medical Oncology, Hospital of Parma
2Medical Oncology, Hospital of Urbino
3Laboratory Medicine.
4Medical Oncology.
5Histopathology Hospital of Pesaro, Italy

Prof S. Cascinu Medical Oncology Hospital of Parma Via Gramsci 14 43100 Parma Italycascinu{at}yahoo.com

BACKGROUND:: 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.

PATIENTS AND METHODS:: 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.

RESULTS:: 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 tuniors (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).

CONCLUSIONS:: 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 theTS status.

adjuvant chemotherapy, colorectal cancer, S-phase fraction, thymidylate synthase, vascular endothelial growth factor


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