Overexpression of cyclin D1 mRNA in colorectal carcinomas and relationship to clinicopathological features: Anin situ hybridization analysis

[摘要] Increased expression of a key cell cycle regulator, cyclin Dl, may have relevance to carcinogenesis and clinicopathological characteristics of some cancers. This study represents the first application ofin situ hybridization, ISH, to detect cyclin Dl mRNA in tissue sections from colorectal carcinomas. This approach was selected because of its unique potential to clarify whether increased expression of cyclin Dl mRNA correlates with clinical and pathological parameters. The ISH of a non-radioactive oligonucleotide probe (Biogenex) was immunocytochemically detected in paraffin embedded sections from biopsy or resection specimens. Tumors ranged from well to poorly differentiated, and from stages A, B, C, and D. Ten year survival data were available on the majority of patients. Intensity of tumor and background (smooth muscle) signals were independently scored from 0 to 3. Overexpressed cyclin Dl mRNA was seen in 86% of cases compared to back-ground. This frequency is similar to that reported for pancreatic carcinoma. The average signal intensity score in tumor foci was 1.9 with a background score of 0.05 (p < 001). All cases showed specific staining judged by the cytoplasmic localization and a tumor signal:background ratio > 1. Expression did not differentiate cancers based on grade, stage or survival (p>l), but did differentiate carcinoma and severe dysplasia from mild dysplasia. We conclude that ISH of cyclin Dl mRNA is an effective and relatively specific means of detecting activity of this gene in colonic neoplasms. The high frequency of overexpression implies that gene activity by itself is not likely to predict a tumor’s biological or clinical behavior. On the other hand, these data suggest that increased cyclin Dl gene activity may be an early event in colorectal carcinogenesis. They also are consistent with findings showing cyclin Dl is inducible by a variety of oncogene products.

[学科分类] 生理学与病理学

[关键词] stage