Perineural invasion of prostate carcinoma cells is associated with reduced apoptotic index

Prostate carcinoma is often associated with perineural (PN) invasion. The common occurrence of this phenomenon has led to speculation regarding the mechanisms of this association, yet to date there have been no studies that clearly define biologic differences between PN and nonperineural (NPN) carcinoma cells. To explore the mechanisms underlying PN invasion by prostate carcinoma cells, the authors investigated the influence of neural components on the growth potential of prostate carcinoma cells.

Proliferative and apoptotic activities of PN and NPN carcinoma cells were analyzed on whole-mount sections of human prostates using immunohistochemical techniques in conjunction with a polyclonal Ki-67 antiserum, and the terminal deoxynucleotidyl transferase (TdT) mediated dUTP biotin nick end labeling (TUNEL) technique, respectively.

The proliferative index (Ki-67 positive cells per 100 carcinoma cells) of PN carcinoma cells (median, 4.10) was higher than that of their intraprostatic, NPN counterparts (median, 3.25), although the difference was not statistically significant (median difference, 0.38; 95% confidence interval [CI] = -0.99 to 1.32; P = 0.52). In contrast, the apoptotic index (AI = apoptotic bodies per 1000 carcinoma cells) in the NPN carcinoma cells was significantly lower (median, 4.10), than the PN carcinoma cells (median, 7.23) with a median difference of -3.45 (95% CI = -5 to -1.39; P = 0.02). The authors also found that AI was lower in the carcinoma cells surrounding nerves with a large diameter (P = 0.0005).

These results suggest that PN invasion by prostate carcinoma cells may not be only a volume effect of growing carcinomas; the neural components may favor the growth of carcinoma cells by inhibiting apoptosis, presumably through a paracrine mechanism, and thereby facilitate the spread of carcinoma cells along nerves. The data also suggest that heterogeneity in growth potential of prostate carcinoma cells may be determined by their local microenvironments, such as an association with neural components.