Clinical

Primary tumor removal increases vascular density in liver metastases

Last Updated: 2004-11-09 15:22:34 -0400 (Reuters Health)

By Anne Harding

NEW YORK (Reuters Health) - Vascularization of liver metastases from colorectal cancers increases after the primary tumor is removed, Dutch researchers have found.

Earlier studies confirmed that, in animals, primary tumors inhibit metastases growth by releasing antiangiogenic factors. This is the first evidence for a similar phenomenon in humans.

"Our results strongly suggest that there is an inhibitory effect of the primary tumor on the vascular density of the secondaries," Dr. Robert M.W. de Waal of the University Medical Center Nijmegen and colleagues write. "Whether the mechanism of primary tumor induced growth inhibition in humans is comparable to that observed in animal models remains to be resolved."

Dr. de Waal and his team report their findings in the November 20th issue of the International Journal of Cancer.

The study population included 56 patients with colorectal liver metastases divided into four groups: 21 who underwent biopsies of liver metastases when their primary tumor was removed; 16 whose synchronous metastases were removed at least 6 weeks after resection of the primary tumor; 15 with metachronous liver metastases (metastases that appeared at least 6 months after removal of the primary tumor); and 4 patients who underwent biopsies of liver metastases taken before and after primary tumor removal.

The researchers tested peritumoral vascular density by staining for the endothelial antigen CD31, while staining for CD34 was used to determine intratumoral vascular density.

Among patients with the primary tumor in situ, 71% showed poor to moderate peritumoral vascularization of liver metastases, while 29% had highly vascularized liver tumors. But among patients with synchronous metastases whose primary tumor had already been removed, 63% had a highly vascularized peritumoral area, while 80% of metachronous liver metastases were highly vascularized.

Patients with synchronous or metachronous metastases who had undergone removal of the primary tumor also showed greater intratumoral blood vessel density than those who had not yet undergone primary tumor resection.

In the four patients for whom pre- and post- primary tumor removal biopsies were available, three showed an increase in peritumoral vascular density while all four showed a 23% to 300% increase in intratumoral vessel density.

"Based on our results, it seems important to either remove metastases at the same time as the primary, or start adjuvant therapy aimed at inhibiting angiogenesis already in advance," Dr. de Waal told Reuters Health.

"For physicians it is important to realize that not all tumors are angiogenesis-dependent," he added. "Before starting angiogenesis inhibition trials, they need to know that the tumor type they want to treat is really dependent on angiogenesis for its growth."

Int J Cancer 2004;112:554-559.