Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Abstract

Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p 5 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p 5 0.02) and pN (p 5 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p 5 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni-and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. ' 2006 Wiley-Liss, Inc.Key words: renal cell carcinoma; cyclin B1; prognosis Renal cell carcinoma (RCC), accounts for 3% of human malignancies in western countries. 1 The incidence of RCC has increased during the past decades, at least in part due to the widespread availability of imaging modalities such as ultrasonography or computerized tomography during evaluation of abdominal and gastrointestinal complaints, thus resulting in a higher frequency of incidentally diagnosed, but still organ-confined tumors. 2 Though surgery offers the chance to cure localized disease, therapy for metastatic disease remains inadequate. 3 While RCC can be considered as widely resistant towards chemo-and radiotherapy, the application of systemic immunotherapy results in a limited and in most cases disappointing clinical response. However, both a better understanding of molecular processes involved in carcinogenesis 3 as well as the introduction of molecular-targeted agents are expected to improve the efficacy of future treatment modalities that can be offered to patients with metastasized RCC. [4][5][6][7][8][9] Uncontrolled cell division is one of the key features of tumor cells. Cyclins and cyclin-dependent kinases (cdk) play an important role in the passage of cells through the cell cycle. 10,11 The early phase of the cell cycle that includes the G1 and S ...

miR-379 Regulates Cyclin B1 Expression and Is Decreased in Breast Cancer

“…It has a crucial role in regulating Cyclin-dependent kinase 1 (Cdk1), which initiates the progression from G2 phase to mitosis [15]. Over-expression of Cyclin B1 is associated with a number of different cancers including breast [8,11,16], oesophageal squamous cell [17,18], non-small cell lung [19,20] and renal cancer [21]. Further, over-expression of Cyclin B1 is associated with poor patient survival and increased resistance to radiotherapy in head and neck squamous cell carcinoma [22,23].…”

Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

“…This overexpression has been observed in several human solid tumors, for example, breast cancer (BC), malignant melanoma (MM), and renal cell carcinoma (RCC) [8, 10–12], as well as some hematological cancers [13]. In normal cells, cyclin B1 is restricted to the nucleus, whereas it accumulates in the cytoplasm in tumor cells [8, 14].…”

High cyclin B1 expression is associated with poor survival in breast cancer

“…Cyclin B1 overexpression is common in several cancers (Murakami et al, 1999;Soria et al, 2000;Nozoe et al, 2002;Takeno et al, 2002;Yoshida et al, 2004;Ikuerowo et al, 2006). It has been shown to associate with high-grade tumours and advanced stage of disease, as well as poor prognosis, in several cancers including oesophageal squamous cell (Murakami et al, 1999;Nozoe et al, 2002;Takeno et al, 2002), non-small cell lung (Soria et al, 2000;Yoshida et al, 2004) and renal cell cancer (Ikuerowo et al, 2006).…”

“…It has been shown to associate with high-grade tumours and advanced stage of disease, as well as poor prognosis, in several cancers including oesophageal squamous cell (Murakami et al, 1999;Nozoe et al, 2002;Takeno et al, 2002), non-small cell lung (Soria et al, 2000;Yoshida et al, 2004) and renal cell cancer (Ikuerowo et al, 2006).…”