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.

Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. H&E stain.

Significance

Cancers with PNI usually have a poorer prognosis,[1] 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.[2]

Prostate cancer

In prostate cancer, PNI in needle biopsies is poor prognosticator;[1] however, in prostatectomy specimens it is unclear whether it carries a worse prognosis.[3]

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.[4] 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.[5]

Additional images

See also

References
  1. Potter, SR.; Partin, AW. (2000). "The significance of perineural invasion found on needle biopsy of the prostate: implications for definitive therapy". Rev Urol. 2 (2): 87–90. PMC 1476100. PMID 16985741.
  2. Gillespie, Shawn; Monje, Michelle (2020). "The Neural Regulation of Cancer". Annual Review of Cancer Biology. 4: 371–390. doi:10.1146/annurev-cancerbio-030419-033349.
  3. Bostwick, DG.; Foster, CS. (Nov 1999). "Predictive factors in prostate cancer: current concepts from the 1999 College of American Pathologists Conference on Solid Tumor Prognostic Factors and the 1999 World Health Organization Second International Consultation on Prostate Cancer". Semin Urol Oncol. 17 (4): 222–72. PMID 10632123.
  4. Merrilees, AD.; Bethwaite, PB.; Russell, GL.; Robinson, RG.; Delahunt, B. (Sep 2008). "Parameters of perineural invasion in radical prostatectomy specimens lack prognostic significance". Mod Pathol. 21 (9): 1095–100. doi:10.1038/modpathol.2008.81. PMID 18500264.
  5. Cervantes-Villagrana RD, Albores-García D, Cervantes-Villagrana AR, García-Acevez SJ (18 June 2020). "Tumor-induced Neurogenesis and Immune Evasion as Targets of Innovative Anti-Cancer Therapies". Signal Transduct Target Ther. 5 (1): 99. doi:10.1038/s41392-020-0205-z. PMC 7303203. PMID 32555170.
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