Perineural Invasion: Correlation With Aggressive Phenotype and Independent Prognostic Variable in Both Colon and Rectum Cancer
Authors: Eva M. Poeschl, Marion J. Pollheimer, Peter Kornprat, Richard A. Lindtner, Andrea Schlemmer, Peter Rehak, Michael Vieth, Cord Langner
Journal: Journal of Clinical Oncology (2010)

Liebig et al 1 reported on the clinical significance of perineural invasion (PNI), defined as tumor invasion of nerve structures and spread along nerve sheaths, in colorectal cancer.The authors observed PNI in 30% of rectum and 19% of colon cancers, respectively.In their cohort of 249 patients, presence of PNI was significantly associated with high tumor stage and grade as well as incidence of metastatic disease at time of diagnosis.Moreover, the authors reported PNI to function as an independent predictor of disease-free and cancer-specific survival.We compliment Liebig et al on this contribution, which illustrates that, in a time of increasing focus on molecular prognostic and predictive factors, parameters that are easily assessable during routine work-up of cancer specimens are still valuable in terms of identifying patients at high risk of disease recurrence and cancer-related death.In their investigation, however, presence of PNI was not correlated with other well-documented histopathologic indicators of aggressive tumor behavior, and survival is not separately assessed in colon and rectum cancers.In our experience of 381 patients with colorectal cancer (representing a 5% random sample of the colorectal cancer database of the Institute of Pathology, Medical University of Graz, Graz, Austria), PNI was noted in 31 (13%) of 232 colon and 27 (18%) of 149 rectum cancers on review pathology.In accordance with Liebig et al, 1 presence of PNI was significantly associated with high tumor classification, poor tumor differentiation, presence of nodal disease at time of diagnosis, and International Union Against Cancer tumor stage.In addition, we noted a significant association between PNI and several histopathologic variables indicating aggressive tumor behavior, such as lymphatic invasion, venous invasion, and tumor growth pattern according to Jass et al, 2 as well as the amount of tumor budding, which was assessed at 250ϫ magnification by counting tumor "buds" (ie, isolated single cancer cells and clusters composed of fewer than five cancer cells) at the invasion front. 3Patients with PNI-positive cancers were more likely to experience incomplete tumor resection.Thus PNI was observed in 12% of cases with complete resection (R0) and in 63% of cases with histologically proven incomplete resection (R1).In cases with questionable margin status (RX), PNI was observed in 38% of cases (Table 1).Follow-up data were available for 350 patients (92%).Median follow-up was 45 months (mean, 56 months; range, 0 to 180 months).Adjuvant chemotherapy had been adjusted to N classification.Thus patients with node-positive tumors (or with tumor progression during follow-up) received chemotherapy according to the Mayo regimen (fluorouracil plus leucovorin). 4At the time of last follow-up, 173 patients (49%) showed no evidence of disease.Progressive disease was observed in 141 patients (40%), including 117 patients (33%) who