We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immunohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and.002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and.004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.

Objective MRI features that correlate with histopathologic findings can be identified and used to evaluate extramural vascular invasion on preoperative images. The MRI extramural vascular invasion score provides additional staging information, which is important when selective neoadjuvant therapy is being considered.

As the ability of CT to identify node status is poor, the depth of tumour invasion beyond the muscularis propria is the most accurate way to identify patients with a poor prognosis who may be suitable for neoadjuvant treatment.

Whilst imaging of poor prognostic features in rectal cancers has assisted pre-operative treatment stratification, such features have yet to be evaluated in colonic cancers. This study aims to develop criteria for identifying poor prognostic features in colonic tumours and assess the accuracy of CT prediction against histopathology. Criteria were developed for predicting T-stage and N-stage, the presence of extramural vascular invasion and involvement of the retroperitoneal surgical margin (RSM). These criteria were tested on 33 patients with colonic cancer who underwent pre-operative high-resolution CT of their tumour. Two radiologists (Obs 1 and Obs 2) identified independently these poor prognostic features and the results were compared with the final histopathological results. Histological agreement and interobserver variation were calculated using the kappa test. Accuracy of CT prediction of tumour extension beyond muscularis propria was 82% (Obs 1) and 70% (Obs 2). Correct prediction of RSM involvement was 76% (95% confidence interval (CI): 57.8-88.9%) and 79% (95%CI: 61.1-91%) for Obs1 and Obs 2, respectively, with significant agreement between observers (kappa = 0.455, p = 0.050). Prognosis was correctly predicted using CT in 82% (95%CI: 61.5-81.2%) (Obs1) and 85% (95%CI: 68.1-94.9%) (Obs2) with moderate agreement (kappa = 0.459, kappa = 0.527, respectively) with histology. In conclusion, CT has potential as the imaging modality of choice in the pre-operative prediction of poor prognostic features in colonic cancers and could play a role in future treatment stratification.

Paraffin wax sections of 70 surgically resected colorectal adenocarcinomas were examined for the overexpression of HER2/ c-erbB-2 oncoprotein using three different specific antibodies and the avidinbiotin immunoperoxidase technique. The patients included 38 men and 32 women aged between 47 and 80 years. The tumours were derived from various parts of the large intestinal tract, and represented all three stages of Dukes' classification and the three histological grades of differentiation. Many tumour sections also included adjacent normal or transitional mucosa. Eight tubular adenomas found in the colectomy specimens in association with some carcinomas were also examined. No positive membrane staining was seen in any of the 70 carcinomas, four adenomas, two hyperplastic polyps, nor in the adjacent normal or transitional mucosa.