Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Abstract

Summary Cyclin Dl is a cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumour types as a consequence of gene amplification or chromosomal rearrangements. We analysed the expression of cyclin Dl in 75 patients with transitional cell carcinoma (TCC) to investigate the possible relationship between its expression and clinical outcome as well as histopathological findings using the immunohistochemical method. We observed strong staining (++, > 50% positive cells) for cyclin Dl in 19 cases (25.3%) and weak staining (+, 5-50% positive cells) in 19 cases (25.3%). Overexpression of cyclin Dl was not associated with tumour invasion. No significant association was found between overexpression of cyclin Dl and tumour grade (P > 0.05). We assessed the differences of disease-free interval in superficial tumours and actuarial survival probability in invasive tumours according to the status of cyclin Dl expression. Tumours with (++) staining for cyclin Dl recurred much more rapidly than (-) and/or (+) staining tumours (P < 0.01 for -vs ++; P < 0.05 for + vs ++). However, overexpression of cyclin Dl was not associated with a shortened overall survival of patients with invasive tumours (P< 0.1). These results suggest that genetic alteration of cyclin Dl appears to be an early event in the tumorigenesis of bladder TCC and is associated with early recurrence in superficial tumours.

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

“…It was previously reported that overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers. 11 The results of that study, however, are hampered by the heterogeneous treatment of patients. Moreover, the presence of 50% positive cells was used as the cutoff to define cyclin D1 overexpressing tumors.…”

“…6 It has been shown to correlate with low-grade, low-stage and papillary tumor growth in primary bladder carcinomas, 9,10 and it has been suggested to play an important role in bladder cancer progression. 11 However, the prognostic significance of cyclin D1 expression in urinary bladder cancer has not yet been determined. 12 Evaluation of Ki67, a proliferation-related antigen, using the MIB-1 antibody has been reported to have a prognostic significance in bladder cancer.…”

Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer

“…Immunohistochemical staining was performed by the method previously described (Shin et al, 1997). Briefly, representative tissue sections from 69 cases were deparaffinized and rehydrated.…”

“…Some of the human primary cancers have been found to have amplification or overexpression of the relevant gene locus of cyclin D1 including breast (Gillett et al, 1994;McIntosh et al, 1995;Simpson et al, 1997), oesophagus (Jiang et al, 1992;Adelaide et al, 1995), liver (Zhang et al, 1993;Nishida et al, 1994), head and neck (Callender et al, 1994, Michalides et al, 1995 and urinary bladder cancers (Proctor et al, 1991;Shin et al, 1997).…”

Induced expression of human CCND1 alternative transcripts in mouse Cyl‐1 knockout fibroblasts highlights functional differences

“…22 Further expression of cyclin D1 in tumours detected by immunohistochemical staining has been associated with patient prognosis in a number of cancers including, breast, squamous cell carcinoma of the head and neck (SCCHN), lung, pancreatic and bladder cancer. [23][24][25][26][27] Until recently, less consideration has been given to the function of the protein product from CCND1 trb . Sawa et al 28 have demonstrated that when overexpressed in human malignant glioma cells, the alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.…”