Perineural invasion
In pathology, perineural invasion, abbreviated PNI, refers to the invasion of cancer to the space surrounding a nerve. It is common in head and neck cancer, prostate cancer and colorectal cancer. Significance. Cancers with PNI usually have a poorer prognosis, as PNI is thought to be indicative of perineural spread, which can make resection of malignant lesions more difficult. Cancer cells use nerves as routes of metastasis, which could explain why PNI is associated with poorer outcomes. Prostate cancer. In prostate cancer, PNI in needle biopsies is poor prognosticator; however, in prostatectomy specimens it is unclear whether it  carries a worse prognosis. In one study, PNI was found in approximately 90% of radical prostatectomy specimens, and PNI outside of the prostate, especially, was associated with a poorer prognosis. However, there exists controversies about whether PNI has prognostic significance toward cancer malignancy. In perineural invasion, cancer cells proliferate around peripheral nerves and eventually invade them. Cancer cells migrate in response to different mediators released by autonomic and sensory fibers. Tumor cells secrete CCL2 and CSF-1 to accumulate endoneurial macrophages and, at the same time, release factors that stimulate perineural invasion. Schwann cells release TGFβ, increasing the aggressiveness of cancer  cells through TGFβ-RI. Schwann cells drive perineural invasion, cancer cells interact directly with Schwann cells via NCAM1 to invade and migrate along nerves.