Expression of cyclin d 1 and p 27 as proliferation markers in human bladder cancer

Abstract EN

The study of the cell cycle regulation elements represents the most reliable and reproducible method in the assessment of tumors.

Cyclin Dl forms a holoenzyme with a cyclin-dependent kinase.

It promotes progression through the Gl phase of the cell cycle and so it regulates Gl progression in cancer cells and is overexpressed in various malignant neoplasms including bladder cancer.

As a result, it is a potential target for cancer therapeutics.

The cyclin-dependent kinase inhibitor p2 7 (Kipl) is a powerful molecular determinant of cell cycle progression and is considered to be a tumor suppressor gene.

Loss of expression ofp27 (Kipl) has been shown to be predictive of disease progression and a negative prognostic marker in malignant tumours.

Aim of the present work is to identify the alterations in the balance between p27 gene and cyclin Dl protein in bladder cancer, to understand their impact in tumor progression, and to assess the relation between their expression and other prognostic parameters.

This study included 48 patients with bladder carcinoma including 24 cases with transitional cell carcinoma (TCC: 10 Bilharzial and 14 non-Bilharzial) and 24 cases with squamous cell carcinoma (SCC: 15 Bilharzial and 9 non-Bilharzial).

Immunohistochemical analysis for both cyclin Dl and p27 were carried out on paraffin-fixed sections of neoplastic bladder tissues.

Cyclin Dl was expressed in 70.8% of cancer bladder cases.

There was a statistical significant correlation between percentage of positively stained tumour cells by cyclin Dl and each of the clinical stage (stage T3 vs other stages) and growth pattern (papillary vs solid) of TCC.

There was statistically insignificant association between TCC grade and the cyclin Dl expression.

There was a statistically significant correlation between tumour grade of SCC and cyclin Dl expression.

There was no statistical correlation between cyclin Dl expression and clinical stage of squamous carcinoma.

There was no significant statistical correlation between immunostaining by p27 marker and either growth pattern (papillary vs solid), tumour grade either in transitional cell carcinoma or in squamous cell carcinoma, or clinical stage of invasive TCC or invasive SCC.

The frequency of both Cyclin Dl and p27 expression was higher in Bilharzial associated tumours than in non Bilharzial ones..

In TCC, the cyclin Dl expression in Schistosoma-associated bladder cancer (SABC) was 90% vs.

78.5% non-Schistosoma-associated bladder cancer (NSABC), whereas in SCC, cyclin Dl was expressed in 60% of SABC cases vs.

55.55% NSABC cases.

Similar results were also noticed for the p27 expression.

In TCC, SABC, it was 70% vs.

57.14% in NSABC.

And, p27 positivity in SCC was 66.66% in SABC vs.

77.77%> in NSABC.

Conclusion: Cyclin Dl expression is a frequent event in early neoplastic transformation of the urothelium.

Accordingly, the immunohistochemical evaluation of p27 and cyclinDl expression might be useful in selecting subgroups of patients with a poor prognosis who can be treated with more aggressive modalities.