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

Don Kristt*, Isaac Turner, Rumelia Koren, Edward Ramadan, Rivka Gal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Increased expression of a key cell cycle regulator, cyclin D1, may have relevance to carcinogenesis and clinicopathological characteristics of some cancers. This study represents the first application of in situ hybridization, ISH, to detect cyclin D1 mRNA in tissue sections from colorectal carcinomas. This approach was selected because of its unique potential to clarify whether increased expression of cyclin D1 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 D1 mRNA was seen in 86% of cases compared to background. 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 > 1), but did differentiate carcinoma and severe dysplasia from mild dysplasia. We conclude that ISH of cyclin D1 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 D1 gene activity may be an early event in colorectal carcinogenesis. They also are consistent with findings showing cyclin D1 is inducible by a variety of oncogene products.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalPathology and Oncology Research
Issue number1
StatePublished - 2000
Externally publishedYes


FundersFunder number
MIRTTW00027-05, DK


    • Colon cancer
    • Colorectal carcinoma
    • Cyclin D1
    • Grade
    • In situ hybridization
    • MRNA
    • Stage
    • Survival


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