Clinical relevance of vascular endothelial growth factor-A in colorectal cancer.

PURPOSE: To study the expression status and clinical relevance of vascular endothelial growth factor-A (VEGF-A) in colorectal cancer (CRC) tissues. EXPERIMENTAL DESIGN: VEGF-A expression was investigated by immunohistochemistry in 89 cases with CRC. Some demographic and histopathological variables were compared with VEGF-A expression to determine the prognostic significance in CRC. RESULTS: VEGF-A (-) was found in 24 cases; (+), (++) and (+++) stainings were detected in 24, 35 and six cases, respectively. VEGF-A (-) was found in 20 of 58 cases with left colon cancer, while only four of 31 cases with right colon cancer were VEGF-A (-) (p=0.024). There was a trend for lower tumor grade and lesser serosal invasion in cases with VEGF-A (-) samples (p=0.07 and p=0.079, respectively). Although the correlation was not statistically significant, there was a trend for lower death rate in cases with VEGF-A (-) tumor (p=0.087). The longest survival was found in cases with VEGF-A (-) tumor and the shortest survival was found in cases with VEGF-A (+++) tumor. Median survival for patients with VEGF-A (-), (+), (++) and (+++) tumors was 59, 47, 35 and 11 months, respectively (p=0.02). The Cox proportional hazards model identified stage IV disease and VEGF-A (+++) tumor as having the most important influences upon overall survival (odds ratio: 5.1, 95% confidence interval: 2.0-13.0 and odds ratio: 3.6, 95% confidence interval: 1.0-12.7, respectively), followed by serosal invasion (odds ratio: 2.4, 95% confidence interval: 1.0-5.9). CONCLUSIONS: This study shows that VEGF-A is a poor prognostic factor in cases with CRC, but the relatively small size of the study group precluded the correlation with the entire known prognostic indicator.

Alterations in expression of cartilage-specific genes for aggrecan and collagen type II in osteoarthritis.

PURPOSE: Osteoarthritis is characterized by a progressive degradation of cartilage structure and function. This study tests the hypothesis that disease severity is characterized by alterations in expression of cartilage-specific genes for aggrecan and collagen type II. EXPERIMENTAL DESIGN: Cartilage, discarded from six subjects undergoing knee replacement, was subdivided into homogeneous portions by the surgeon according to the Outerbridge classification. For four subjects, it was possible to separate the tissue into two or three fractions with different disease severity. Portions of each sample were prepared either for histological analysis and ranking according to the Mankin system or for RNA extraction. Quantitative, competitive RT-PCR assays were used for measurement of mRNA for aggrecan, collagen type II, and glyceraldehyde-3-phosphate dehydrogenase. Clinical grading was correlated with histological score (Spearman r=0.60, p=0.043). RESULTS: There was a striking decrease in expression of aggrecan and collagen II that was correlated with increase in the grade in regions of cartilage within an individual subject. In the series of 12 samples, there was an inverse correlation between aggrecan expression and osteoarthritis grade (Spearman r=-0.59, p=0.042). CONCLUSIONS: In conclusion, there was an inverse relationship between regional disease severity in osteoarthritis and expression of aggrecan. Use of quantitative, competitive RT-PCR is practical for assessment of chondrocyte gene signatures.