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Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray
Y Hedberg1, B Ljungberg, G Roos
1Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Abstract:
Aberrations in the G1/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of G1/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D1 and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of G1/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin D1 protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that G1/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes.
Insights
Cell cycle G1/S transition defects are present in renal cell carcinoma (RCC). Low cyclin D1 and p27 levels correlate with aggressive features and poor prognosis in conventional RCC, with distinct patterns across RCC subtypes.
Area of Science:
- Oncology
- Cell Biology
- Molecular Pathology
Background:
- Aberrations in the G1/S cell cycle transition are implicated in various cancers.
- The clinical relevance of G1/S regulatory defects in renal cell carcinoma (RCC) remains under-investigated.
Purpose of the Study:
- To investigate the protein expression of G1/S regulators (cyclin D1, D3, E, p27) in RCC.
- To correlate these findings with clinico-pathological parameters and patient prognosis.
- To explore differences in G1/S regulatory defects among RCC subtypes.
Main Methods:
- Tissue microarray and immunohistochemistry were used to analyze protein expression in 218 RCC samples.
- Western blotting and immunohistochemical staining of regular tissue sections confirmed a subset of results.
- Analysis focused on cyclin D1, D3, E, and p27 protein levels.
Main Results:
- Low cyclin D1 and p27 protein levels were associated with high nuclear grade, larger tumor size, and poorer prognosis in conventional RCC.
- Distinct patterns of G1/S regulatory defects were observed across RCC subtypes.
- Chromophobe RCC generally lacked p27 staining, while conventional RCC often showed high cyclin D1 and papillary RCC showed high cyclin E.
Conclusions:
- G1/S regulatory defects are present in RCC and correlate with clinico-pathological features.
- The specific patterns of cell cycle dysregulation differ significantly among RCC subtypes, suggesting subtype-specific mechanisms.
- These findings highlight the potential of G1/S regulators as prognostic markers and therapeutic targets in RCC.