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Background: Leukocyte telomere length (LTL) is a potential biomarker of cancer prognosis; however, evidence for renal cell carcinoma (RCC) is inconsistent., Methods: We investigated LTL and RCC-specific survival among 684 cases from the US kidney cancer study (USKC) and 241 cases from the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO). Leukocyte telomere length was measured by quantitative polymerase chain reaction, and hazard ratios (HRs) and 95% confidence intervals (CIs) computed using multivariable Cox models., Results: Short LTL was associated with poorer disease-specific survival in both USKC (lowest vs highest quartile: HR: 2.3, 95% CI: 1.2-4.4; P for trend=0.02) and PLCO (HR: 2.4, 95% CI: 1.0-5.4; P=0.04). Among USKC cases, the association was strongest for stage-I RCC (HR: 5.5, 95% CI: 1.6-19.0; P=0.006)., Conclusions: Our findings suggest that shorter LTL is an independent marker of poor RCC prognosis, particularly for stage-I disease.

Despite the significance of tumour neoangiogenesis and the extensive knowledge on the molecular basis of blood vessel formation currently no quantitative data exist on the 3D microvascular architecture in human primary tumours and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events., (Copyright 2001 Cancer Research Campaign.)

Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer.

A bioluminescence technique involving single photon imaging was used to quantify the spatial distribution of the metabolites ATP, glucose and lactate in cryosections of various solid tumours and normal tissue. Each section was covered with an enzyme cocktail linking the metabolite in question to luciferase with light emission proportional to the metabolite concentration. The photons emitted are imaged directly through a microscope and an imaging photon counting system. In some cases, good agreement was observed between the distribution of relatively high concentrations of ATP and glucose in viable cell regions of the periphery, while the reverse was seen in more necrotic tumour centres with comparatively high lactate levels. In general, lactate was distributed more diffusely over the sections while ATP was more highly localised and glucose assumed an intermediate pattern. In contrast to the large degree of heterogeneity seen in tumours, distribution patterns of metabolites were much more homogeneous in normal tissue, such as heart muscle. Mean values for metabolite levels in cryosections using bioluminescence are in good agreement with those obtained from the same tumour by conventional methods.

Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides. Five cancers, but no uninvolved mucosa, expressed high-affinity, low-capacity bombesin binding sites (Kd = 6.53 nM, Bmax = 58.6 fmol mg-1 protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8 nM). Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours.

Desmosomes are adhesive junctions of epithelial cells. Their expression may be altered or lost in carcinomas resulting in reduced cellular adhesiveness. The desmosomes of colorectal carcinomas have been studied by fluorescent antibody staining, immunoblotting and electromicroscopy. A series of 58 malignant specimens, comprised of primary tumours and metastases, were desmosome positive. There was no indication of a comparative reduction in desmosome expression that might give rise to reduced adhesiveness of tumour cells, although loss of polarised junctional distribution in poorly differentiated tumours might have such a consequence. Western blotting analysis of colorectal cancers and cultured carcinoma cells identified desmosomal polypeptides dp1 + 2, dg1 and dg2 + 3 with similar relative molecular weights to normal homologues. In addition, a polypeptide of 140,000 was recognised only in malignant epithelium by anti-dg2 + 3 antiserum. The significance of this polypeptide is not understood. Tumours and uninvolved epithelium were exposed to low extracellular [Ca2+] to test whether tumour desmosomes were of reduced stability. This caused much cellular degradation in tumours but some viable cell clumps possessed desmosomes resistant to disruption by low [Ca2+]. Desmosomes may thus have a positive role in metastasis by maintaining intercellular adhesion between metastasising cells.