Reuters Health Information (2004-11-09): Primary tumor removal increases vascular density in liver metastases
Primary tumor removal increases vascular density in liver metastases
Last Updated: 2004-11-09 15:22:34 -0400 (Reuters Health)
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
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
"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.