Biological Significance of Perineural Invasion (PNI) in Prostate Cancer

Background: In order to better understand the biological significance of perineural invasion (PNI) in prostate cancer, we aimed to analyze in situ the expression of molecules involved in tumor growth or nerve trophicity.

Methods: Tissues from 66 radical prostatectomies performed for prostate cancer (40 with PNI and 26 without PNI) were selected and included in a tissue microarray (TMA): PNI areas (when available), cancer far from nerves, and nerves far from cancer. The expression of the following molecules was analyzed using immunohistochemistry on TMA slides: macrophage migration inhibitory factor (MIF) and its receptor CD74, EGF receptor (EGFR), heregulin (HRG) and its receptor ErbB3, and the proliferation marker Ki67.

Results: Cancer cells in the PNI areas showed increased proliferation, EGFR and CD74 expression, when compared to cells far from nerves (P = 0.009, 0.0005, and 0.02, respectively). Moreover, cell proliferation and CD74 staining were increased in cancers with PNI features compared to cancers without PNI (P = 0.001), even when adjusting for Gleason score, tumor size, and pathological stage.

Conclusions: These results suggest that cancer cells in the PNI areas could acquired a growth advantage that could be triggered by the growth factor receptors EGFR and CD74.