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001). Comparable results were noted for intramural and extramural lymphatic invasion (35% versus 64%, PErbB of tumor grade and lymphatic invasion, yet inferior to that of lymph-node metastasis. When analysis was restricted to patients with AJCC/UICC stage II tumors, venous invasion proved to be the only prognostic variable with respect to both PFS (P=0.011) and CSS (P=0.006).41 In node-positive tumors, lymphatic invasion can be identified in only about 50% of cases. The prognostic significance of lymphatic invasion is however limited in this subgroup: T and N classification, as well as tumor differentiation, are the major variables for prognostication, and merit special attention in patient counseling and decision making.42 Venous invasion is widely believed to be an underreported finding, with significant variability in its reported incidence.40 Alisertib solubility dmso However, accurate assessment is crucial and of particular importance in stage II disease, because it may influence the decision to administer adjuvant therapy. In our study, prognostication by review pathology was superior to routine pathology, and both false-positive (mainly due to the overestimation of retraction artifacts) and false-negative diagnoses may occur.41 Some authors stressed that the diagnosis of vascular involvement may be improved by applying ancillary techniques, such as Elastica van Gieson and immunostaining for cluster of differentiation (CD)31 and D2-40 for the detection of endothelial cells, as well as ��-smooth-muscle actin for the detection of vessel walls.35,43 Perineural invasion PNI is defined by tumor-cell invasion of nervous structures, as illustrated by neoplastic invasion of nerves and/or spread along nerve sheaths (Figure 2C).44,45 In some neoplasms, in particular pancreatic and prostate adenocarcinomas, PNI has been recognized as a characteristic histological feature.5,46 Its presence constitutes a process GSK J4 concentration for neoplastic invasion and cancer spread independent of blood and lymphatic vessels. In the pathogenesis of PNI, neurotropic factors and matrix metalloproteinases seem to be involved.45 The prognostic significance of PNI in CRC has been investigated by several groups. Liebig et al46 reported fourfold-greater 5-year disease-free survival rates for patients with PNI-negative cancers compared to patients with PNI-positive cancers (65% versus 16%, P