Primary tumor removal increases vascular density in liver metastases
Last Updated: November 09, 2004



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."





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