Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy.

Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location has an impact on the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal colon cancers is not well established. We investigated the associations between tumor location, KRAS and BRAF mutation status, and the messenger RNA (mRNA) expression of proteins involved in major signaling pathways, including tumor growth (epidermal growth factor receptor (EGFR)), angiogenesis (vascular endothelial growth factor receptor 2 (VEGFR2)), DNA repair (excision repair cross complement group 1 (ERCC1)) and fluoropyrimidine metabolism (thymidylate synthase (TS)). Formalin-fixed paraffin-embedded tumor specimens from 431 advanced CRC patients were analyzed. The presence of seven different KRAS base substitutions and the BRAF V600E mutation was determined. ERCC1, TS, EGFR and VEGFR2 mRNA expression levels were detected by reverse transcriptase-PCR. BRAF mutations were significantly more common in the proximal colon (P<0.001), whereas KRAS mutations occurred at similar frequencies throughout the colorectum. Rectal cancers had significantly higher ERCC1 and VEGFR2 mRNA levels compared with distal and proximal colon tumors (P=0.001), and increased TS levels compared with distal colon cancers (P=0.02). Mutant KRAS status was associated with lower ERCC1, TS, EGFR and VEGFR2 gene expression in multivariate analysis. In a subgroup analysis, this association remained significant for all genes in the proximal colon and for VEGFR2 expression in rectal cancers. The mRNA expression patterns of predictive and prognostic biomarkers, as well as associations with KRAS and BRAF mutation status depend on primary tumor location. Prospective studies are warranted to confirm these findings and determine the underlying mechanisms.

Detection and assessment of intracranial aneurysms: value of CT angiography with shaded-surface display.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of circle of Willis CT angiography with shaded-surface display in the detection and assessment of suspected intracranial aneurysms. MATERIALS AND METHODS: Twenty-three patients who had clinical or radiologic suspicion of intracranial aneurysms were studied prospectively with CT angiography and conventional angiography. The images were obtained and interpreted in a double-blind fashion by different radiologists. Conventional angiography, which was the reference standard in this study, diagnosed 17 aneurysms in 15 patients. The usefulness of the two types of images for surgical planning was evaluated by two neurosurgeons. RESULTS: No aneurysms were detected with either technique in eight patients. Both techniques showed 15 aneurysms in 14 patients. The maximum dimensions were less than 3.0 mm in three cases, 3.0-5.0 mm in four cases, and greater than 5.0 mm in eight cases. With conventional angiography used as the reference standard, CT angiography has one false-positive and two false-negative findings, resulting in a sensitivity of 88% (15/17) and a specificity of 89% (8/9). For 12 of 15 aneurysms, CT angiography was rated equal or superior to conventional angiography in depicting all aspects (shape, orientation, neck, and parent vessel) of the aneurysms. CONCLUSION: We were able to detect aneurysms of the circle of Willis as small as 2 mm in size. Using conventional angiography as the reference standard, CT angiography has a sensitivity of 88% and a specificity of 89% for the detection of aneurysms in the circle of Willis. In almost all cases, CT angiography was equal or superior to conventional angiography in characterizing the aneurysms for surgical planning.