Evidence from a recent study suggests that distant metastases may spread from the primary tumor independently and not through the lymph nodes as traditionally thought.

Current models of cancer transmission represent the evolution of metastases as originating from the primary tumor and spreading to the lymph nodes, then to other organs. Treatment for solid tumors follow a staging scheme called TNM (primary tumor [T], nodal metastasis [N], and distant metastasis [M]). Recently several clinical trials, however, demonstrated that removing the metastatic lymph nodes does not consistently improve patient survival, which led the investigators to question the relationship between nodal and distant metastases. 

Study authors used polyguanine (poly-G) typing to analyze tumor samples from patients with colorectal cancer from primary, nodal, and distant metastases. The poly-G assay is able to identify which areas on the primary tumor is the origin of metastatic tumors based on the genetic profiles.

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They discovered that in 35% of patients, both nodal and distant metastases originated from the primary tumor. In 65% of samples, however, the poly-G typing revealed that nodal and distant tumor cell types were different, indicating that they had independent origins from different cell types within the primary tumor.

The lead investigator, Kamila Naxerova, PhD, concluded by saying, “We now suspect that lymph node metastases simply indicate the presence of an aggressive primary tumor, rather than being directly responsible for the formation of distant metastases. Now we need to investigate whether clinical outcomes for patients whose lymphatic and distant metastases have common origins are different from those of patients whose metastases have distinct evolutionary origins. If there is a difference, our assay might be a useful prognostic test in the future.”


1. Lymph node metastases may not always be the source of cancer’s spread to other organs [news release]. EurekAlert! website. https://www.eurekalert.org/emb_releases/2017-07/mgh-lnm063017.php. Published July 7, 2017. Accessed July 7, 2017.