This was a strong recommendation made by the New South Wales audit of pathology reporting in 2000.14 However, it remains to be seen whether current hospital practice, in both the operating room and the pathology laboratory in both the public and private sectors, adheres to this approach. Currently, the most widely used taxonomy of clinicopathological staging of CRC is the TNM system based on the original recommendations by Pierre Denoix,24,25 and promoted by the UICC. The AJCC mTOR inhibitor recommendations for staging and end-results reporting are based on the principles of TNM.1 Indeed the UICC and AJCC have collaborated closely over many years to produce a uniform, comprehensive, multidimensional

staging classification. An excellent historical overview of this clinicopathological approach is summarised in the current Dabrafenib seventh edition (TNM7) of the AJCC “Cancer Staging Manual” effective for cancers diagnosed on or after January 1, 2010.8 The details of this system as they apply to CRC are beyond the scope of this review but can be readily consulted either in TNM7 or in the abbreviated sixth edition of the AJCC Cancer Staging Handbook26 of the Manual. A general criticism of the TNM format of clinicopathological staging remains the inherent, constantly evolving complexity of this system due to repeated detailed revision every six to eight years, often without adequate levels of evidence.16 Further complexity is added

when a stage is broken down or sub-classified depending on whether the stage is determined following neoadjuvant treatment, or after surgery, or at the time of recurrence or for cancers diagnosed at autopsy. Overall, five stage classifications are described for any particular tumor site including: clinical/pre-treatment stage designated as cTNM or TNM; pathologic stage designated as pTNM; post therapy or post neoadjuvant therapy stage designated as ycTNM or ypTNM and autopsy classification

designated as aTNM.8 This contrasts markedly with the simple stepwise structure of classical Dukes’ or the ACPS system. Within the hierarchy of TNM there are several contentious issues which require emphasis find more and clarification and these are well discussed in a detailed review by Compton.27 Concerning T stage, it should be understood that pTis (carcinoma in situ) refers to both “intraepithelial carcinoma”, that is the presence of malignant cells confined above the basement membrane, and “intramucosal carcinoma” where spread is confined to the lamina propria and not beyond the muscularis mucosae. Hence, penetration of the muscularis mucosae with access of tumor cells to lymphatics and small blood vessels (i.e. pathways for metastatic spread) are classified as pT1. Category pT3 implies direct tumor spread to perimuscular, subserosal soft tissues but not direct involvement of a serosal surface nor infiltration into an adjacent structure.