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Conventionally, lymphatic spread is regarded as the principal mechanism by which haematogenous metastasis occurs in colorectal cancer. The aim of this cross sectional study was to determine the relative strengths of direct tumour spread, the presence of lymph node metastasis and histologically demonstrated venous invasion as drivers of haematogenous metastasis diagnosed at the time of resection of colorectal cancer. The data were drawn from a hospital database of consecutive bowel cancer resections between 1995 and 2017 inclusive. The presence of haematogenous metastasis was determined at the time of surgery by imaging or other investigations or operative findings. Where possible, histological confirmation was obtained. Specimen dissection and reporting followed a standardised procedure. Tumour staging was according to the 7th edition of the UICC/AJCC pTNM system. Analysis was by multivariable logistic regression. After exclusions 3133 patients remained, among whom 380 (12.1%) had one or more haematogenous metastases. In bivariate analyses, the frequency of haematogenous metastasis was directly associated with increasing T status (p

The pTNM staging system for colorectal cancer (CRC) is not entirely effective in discriminating between potentially curative and non-curative resections because it does not account for local residual tumour in patients with stages I, II or III. This study aimed to evaluate the prognostic importance of histologically verified tumour in any line of resection of the bowel resection specimen (TLR) in relation to pTNM stages and to demonstrate how TLR may be integrated into pTNM staging. Information on patients in the period 1995 to 2010 with complete follow-up to the end of 2015 was extracted from a prospective database of CRC resections. The outcome variables were the competing risks incidence of CRC recurrence and CRC-specific death. After exclusions, 2220 patients remained. In 1930 patients with pTNM stages I-III tumour, recurrence was markedly higher in those with TLR than in those without (HR 6.0, 95% CI 4.2-8.5, p 0.001) and this persisted after adjustment for covariates associated with recurrence. CRC-specific death was markedly higher in the presence of TLR (HR 7.7, CI 5.3-11.2, p 0.001), which persisted after adjustment for relevant covariates. These results justify removing patients with TLR from pTNM stages I to III and placing them in stage IV, thereby allowing the categorisation of all patients with any known residual tumour into three prognostically distinct groups. This study demonstrates how TLR may be integrated into pTNM staging, thus improving the definition of the three stages which are considered potentially curable (I, II and III).

Background As a precursor lesion, adenoma is ideally suited for proteome profiling to investigate early colorectal cancer (CRC) development. The ability to recognise premalignant lesions may have important applications in cancer prevention. Aim To identify protein expression patterns that can distinguish colorectal adenoma from normal tissue. Methods Twenty paired samples of adenoma and normal mucosa were analysed by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MALDI-TOF/TOF MS) to detect proteins with ≥ 2-fold differential expression. Protein expression was validated and localised by immunohistochemistry (IHC). Results 2-DE identified four up-regulated (Annexin A3, S100A11, S1 00P and eIF5A-1)and three down-regulated (Galectin-1, S100A9 and FABPL) proteins in adenomas. These proteins have important functions in cell differentiation, proliferation and metabolism.The finding of decreased S100A9 and galectin-1 expression in adenoma was unexpected given the previous reports of their up-regulation in CRC. Our observations however, were validated by IHC and explained by the cellular localisation of these proteins, which are linked to tumour-associated inflammatory and stromal responses respectively, features seen in CRC but not in adenoma. Conclusions Proteomic study of adenomas provides unique biomolecular insights into early colorectal carcinogenesis, however findings need to be validated and interpreted in the light of IHC tissue localisation. This study identifies a distinctive pattern of protein expression that differentiates colorectal adenoma from both CRC and normal mucosa.

Background and aim Increased expression of glutathione S-transferase pi (GSTP) has been shown to be associated with poor prognosis and reduced survival in many cancers. Our study aimed to examine the association between GSTP expression, histopathology and survival in a large consecutive series of patients after potentially curative resection for node-positive stage C colonic adenocarcinoma. Methods and results Nuclear and cytoplasmic GSTP expression in both superficial and deep parts of the tumour were assessed retrospectively by tissue microarray and immunohistochemistry in specimens from 469 patients, whose other histopathology had been recorded in a prospective hospital registry of large bowel cancer resections from 1971 to 2001 with a minimum follow-up of 5 years. The intensity of staining was graded as 0 (no staining), 1 (weak), 2 (intermediate) and 3 (strong). The percentage of cells staining was recorded as 0%, Conclusions GSTP expression is an independent prognostic factor in reduced overall survival in stage C colonic adenocarcinoma.

To determine the biological and prognostic significance of DNA ploidy, 492 consecutive and prospectively documented cases of colorectal cancer were retrieved from the archives of Concord Hospital. 35 cases were excluded due to poor preparations. Nuclei were extracted from paraffin blocks and analysed by DNA flow cytometry. A tumour was classified as diploid when only one G 0 -G 1 peak was detected and aneuploid when there were two or more G 0 -G 1 peaks. The DNA index (DI) was derived from the ratio between the mean fluorescence intensities of the second or aberrant G 0 -G 1 peak and the reference 2N peak. Anatomical Site Diploid Hyperdiploid DI DI ≥ 1.4 Proximal Colon 58 27 37 Distal Colon 56 25 81 Rectum 67 26 80 After a follow-up of 7 years DNA ploidy was of marginal importance as a prognostic indicator (p=0.055). Clinical staging (ACPS), extent of direct tumour spread and extent of lymph node involvement were the most relevant prognostic indicators, once other factors were taken into account. Aneuploidy was also significantly correlated with absence of contiguous adenoma, tumour ulceration and venous invasion. The degree of aneuploidy or DI was greater in distal colorectal (DCR) i.e. splenic flexure and beyond than proximal colon (PC) cancers (p