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Surgery and Hematogenous Dissemination: Comparison Between the Detection of Circulating Tumor Cells and of Tumor DNA in Plasma Before and After Tumor Resection in Rats

¹ Experimental Research Unit, General University Hospital of Albacete, C/ Hermanos Falcó 37, 02006 Albacete, Spain
² Department of Pathology, General University Hospital of Albacete, Albacete, Spain
³ Department of Surgery, Universidad Autónoma de Madrid and La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain

Correspondence: Address correspondence and reprint requests to: Dolores C. García-Olmo, PhD; E-mail: doloresg{at}sescam.jccm.es.

Background: To examine the effects of the surgical manipulation of tumors on the hematogenous dissemination of tumors, we compared rates of detection of tumor-derived DNA in the buffy coat and in plasma from tumor-bearing rats before and after tumor resection.

Methods: We injected DHD/K12-PROb cells subcutaneously into BD-IX rats. Three weeks later, we removed the tumors surgically. Group PERI was sacrificed 3 hours after surgery, group POST-2 was sacrificed 2 weeks later, group POST-4 was sacrificed another 2 weeks later, and group POST-LONG was sacrificed when rats were close to death. In group PERI, four perioperative blood samples were taken. In the other groups, only one blood sample was taken per rat, immediately before euthanasia. We used polymerase chain reaction to detect tumor-derived DNA in buffy-coat, plasma, and lung samples.

Results: In group PERI, tumor DNA in plasma was more frequent than circulating tumor cells at all perioperative time points. The difference was statistically significant 3 hours after surgery (P = .035). In group POST-2, there was no detectable metastasis or tumor DNA in blood samples. There were lymphatic and lung metastases in most animals in group POST-4 and in all animals in group POST-LONG. In the last two groups, the frequencies of tumor DNA in the buffy coat and in plasma were similar.

Conclusions: In our animal model, the hematogenous dissemination of tumors due to surgery seemed to be more closely related to tumor-derived cell-free DNA than to circulating tumor cells. In addition, the surgical resection of primary tumors did not inhibit the development of metastases.

Key Words: Circulating tumor cells • Cell-free tumor DNA • Colon cancer • Surgery • Metastasis