A study led by Massachusetts General Hospital (MGH) investigators has found that the traditional model for the spread of carcinoma, the deadliest form of cancer—from the primary tumor, to nearby lymph nodes, to other organs—may not apply in all cases. In their report in the July 7 issue of Science, the researchers describe finding that, for the majority of colorectal cancer patients in the study, “distant” metastases originated directly from the primary tumor, independent of any lymph node metastases.
“Our results provide the first evidence in humans that the century-old ‘lymph node metastases are precursors of distant metastases’ model does not apply to all or even most colorectal cancers,” says lead and corresponding author Kamila Naxerova, PhD, of the Edwin L. Steele Laboratories for Tumor Biology in the MGH Department of Radiation Oncology. “These findings fill an important gap in our knowledge of metastatic disease evolution and have the potential to guide improvements in the clinical management of lymph node metastases.”
The current study is a follow-up to a 2014 report in which Naxerova and her colleagues described a simple assay that could reveal evolutionary relationships between tumors at various sites in a patient’s body. Based on analysis of small, mutation-prone segments of the genome called polyguanine (poly-G) repeats, that study found that relationships between primary and metastatic tumors were different in each case—for example, in some patients metastatic spread occurred early and in others late in tumor development. The assay was also able to identify specific areas within a primary tumor that had been the source of specific metastases, based on their genetic profiles.
Treatment for most solid tumors now incorporates what are called TNM—primary tumor (T), nodal metastasis (N), and distant metastasis (M)—staging schemes. Patients with lymph node metastases are known to have a higher likelihood of developing distant metastases, implying a link between the two. But in several recent clinical trials the removal of metastatic lymph nodes did not always improve patient survival, casting doubt on the relationship between nodal and distant metastasis. To better understand relationships between primary tumors and the two types of metastases, the researchers used poly-G typing to analyze more than 200 tissue samples of primary tumors, lymph node metastases and distant metastases from 17 patients with colorectal cancer.
Source: Medical Xpress
