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Am J Surg Pathol. 2016 Jan;40(1):103-12. doi: 10.1097/PAS.0000000000000518.

Perineural Invasion is a Strong Prognostic Factor in Colorectal Cancer: A Systematic Review.

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Departments of *Pathology †Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.


Perineural invasion (PNI) is a possible route for metastatic spread in various cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis, but systematic analyses are lacking. This study systematically reviews the frequency and impact of PNI in CRC. A literature search was performed using PubMed database from inception to January 1, 2014. Data were analyzed using Review Manager 5.3. A quality assessment was performed on the basis of modified REMARK criteria. Endpoints were local recurrence (LR), 5-year disease-free survival (5yDFS), 5-year cancer-specific survival (5yCSS), and 5-year overall survival (5yOS). Meta-analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). In this meta-analysis, 58 articles with 22,900 patients were included. PNI was present in 18.2% of tumors. PNI is correlated with increased LR (RR 3.22, 95% CI, 2.33-4.44) and decreased 5yDFS (RR 2.35, 95% CI, 1.66-3.31), 5yCSS (RR 3.61, 95% CI, 2.76-4.72), and 5yOS (RR 2.09, 95% CI, 1.68-2.61). In multivariate analysis PNI remains an independent prognostic factor for 5yDFS, 5yCSS, and 5yOS (HR 2.35, 95% CI, 1.97-3.08; HR 1.91, 95% CI, 1.50-2.42; and HR 1.85, 95% CI, 1.63-2.12, respectively). We confirmed the strong impact of PNI for LR and survival in CRC. The prognostic value of PNI is similar to that of well-established prognostic factors as depth of invasion, differentiation grade, lymph node metastases, and lymphatic and extramural vascular invasion. Therefore, PNI should be one of the factors in the standardized reporting of CRC and might be considered a high-risk feature.

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