Expression of the cell cycle proteins p21, p27, and pRb in clear cell renal cell carcinoma and their prognostic significance

Haitel, Andrea; Wiener, H.; Neudert, Barbara; Marberger, Michael; Susani, Martin

doi:10.1016/s0090-4295(01)01188-8

Cited by 45 publications

(40 citation statements)

References 11 publications

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“…In multivariate analysis, p27 expression was the strongest predictor of survival for HCC patients, which was independent of the other variables. Similar findings have also been observed in other cancers [32][33][34] . It is therefore suggested that p27 should work as a negative regulator during hepatocarcinogenesis and may exert a useful prognostic marker.…”

Section: Discussionsupporting

confidence: 90%

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma

Kang

Zhao²,

Gong³

2004

WJG

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AIM:To investigate p27 expression in hepatocellular carcinoma (HCC), adjacent nontumoral and normal liver tissues, and to verify whether the subcellular localization of p27 was altered in HCC. METHODS:The level of p27 in tumoral, nontumoral, and normal liver tissues were assessed by immunohistochemical (IHC) analysis. Parallel immunostaining was done for proliferating cell nuclear antigen (PCNA) to evaluate cell proliferation.

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Section: Discussionsupporting

confidence: 90%

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma

Kang

Zhao²,

Gong³

2004

WJG

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“…The absent correlation between p27 Kip1 protein levels and tumor grade as observed in the present investigation confirmed the outcome of three previous studies that included a total number of 244 different RCC specimens [11][12][13] . In contrast, p27 Kip1 positivity was also described to decrease when histological dedifferentiation increased (total number of patients investigated in two studies: 372) [14,15] .…”

Section: Discussionsupporting

confidence: 92%

“…Kip1 protein levels not to be correlated with tumor stage [11,12,14] . In contrast, one report described a significant difference for p27…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous p27<sup>Kip1</sup> Expression within Primary Renal Cell Cancers, Their Invasive Margins and Peritumoral Renal Parenchyma Correlation with Pathological and Prognostic Features

Merseburger

Serth²,

Heyde³

et al. 2007

Urol Int

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Introduction: The expression of the negative cell cycle regulator p27^Kip1 is frequently found to be deregulated in various human cancer types. Whether expression of p27^Kip1 can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. Patients and Methods: For analysis of p27^Kip1 in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. Results: In univariate survival analysis, decreased expression of p27^Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients’ disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27^Kip1 protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27^Kip1 (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. Conclusion: Our analysis demonstrated that p27^Kip1 is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27^Kip1 protein expression for patients diagnosed with renal cell carcinoma.

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“…Hui et al [26]demonstrated that, in hepatocellular carcinoma, not only the lack of pRb expression but also its overexpression were observed especially in cases of biologically aggressive phenotypes such as poor differentiation and large tumor size. In ovarian carcinoma, renal carcinoma, and non-Hodgkin malignant lymphoma, increased pRb expression predicts poorer patient outcomes [27, 28, 29]. One hypothesis may be that the pRb being overexpressed in papillary microcarcinoma with clinically apparent metastasis is dysfunctional, for example, hyperphosphorylated because of the overexpression of cyclins, including cyclin D1, or the presence of alteration in the upstream genes that regulate pRb expression.…”

Section: Discussionmentioning

confidence: 99%

Papillary Microcarcinomas of the Thyroid with Preoperatively Detectable Lymph Node Metastasis Show Significantly Higher Aggressive Characteristics on Immunohistochemical Examination

et al. 2005

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Objectives: We recently demonstrated that papillary microcarcinomas with preoperatively detectable node metastasis in the lateral compartment on ultrasonography (clinically apparent metastasis) show worse postoperative relapse-free survival than those with no metastasis or metastasis that could not be detected preoperatively, but was confirmed by pathological examination after surgery (occult metastasis). In this study, we investigated difference in the aggressive characteristics of microcarcinoma of this type from various perspectives. Materials and Methods: We immunohistochemically examined the expression of cell proliferating markers, Ki-67, cyclin D1, p27, and retinoblastoma gene product (pRb), apoptotic markers, single-strand DNA (ssDNA), and metastatic suppressor, kangai-1 (KAI-1) for 19 microcarcinoma patients with clinically apparent metastasis, 14 patents with occult metastasis, and 22 patients without metastasis. Results: Cases of clinically apparent metastasis showed increased cyclin D1 expression together with decreased p27 expression and higher levels of pRb and Ki-67 expression. Furthermore, ssDNA expression was higher and bcl-2 expression was lower in these cases, while KAI-1 expression was significantly reduced. There was no significant difference in the expression of these proteins between cases demonstrating no and occult metastases. Conclusion: These findings suggest that cases of clinically apparent metastasis show significantly higher growth based on cell proliferating activity, apoptosis, and expression of metastatic suppressor than those demonstrating no or occult metastases.

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Expression of the cell cycle proteins p21, p27, and pRb in clear cell renal cell carcinoma and their prognostic significance

Cited by 45 publications

References 11 publications

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma

Heterogeneous p27<sup>Kip1</sup> Expression within Primary Renal Cell Cancers, Their Invasive Margins and Peritumoral Renal Parenchyma Correlation with Pathological and Prognostic Features

Papillary Microcarcinomas of the Thyroid with Preoperatively Detectable Lymph Node Metastasis Show Significantly Higher Aggressive Characteristics on Immunohistochemical Examination

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Expression of the cell cycle proteins p21, p27, and pRb in clear cell renal cell carcinoma and their prognostic significance

Cited by 45 publications

References 11 publications

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27Kip1in hepatocellular carcinoma

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27Kip1in hepatocellular carcinoma

Heterogeneous p27<sup>Kip1</sup> Expression within Primary Renal Cell Cancers, Their Invasive Margins and Peritumoral Renal Parenchyma Correlation with Pathological and Prognostic Features

Papillary Microcarcinomas of the Thyroid with Preoperatively Detectable Lymph Node Metastasis Show Significantly Higher Aggressive Characteristics on Immunohistochemical Examination

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Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma

Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27^Kip1in hepatocellular carcinoma