Expression of the secreted form of clusterin protein in renal cell carcinoma as a predictor of disease extension

Kurahashi, Toshifumi; Muramaki, Mototsugu; Yamanaka, Kazuki; Hara, Isao; Miyake, Hideaki

doi:10.1111/j.1464-410x.2005.05733.x

Cited by 61 publications

(43 citation statements)

References 20 publications

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“…Although this study showed an association between high cytoplamic clusterin and adverse outcome for stage II colorectal cancer, there are conflicting data regarding the prognostic importance of this protein in different cancer types (17)(18)(19)(20)(21)(22)(23); some studies associate high clusterin levels with poor outcome (17)(18)(19)(20)(21) and others with a good prognosis (22,23). This may be related to a number of clinical and technical factors.…”

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 82%

“…Several studies have examined the prognostic significance of clusterin in human cancer with conflicting results. Cytoplasmic clusterin expression correlates with poor prognosis in prostate adenocarcinoma (17), renal cell carcinoma (18), ovarian carcinoma (19), cervical cancer (20), and hepatocellular carcinoma (21). In contrast, cytoplamic clusterin expression correlates with a good prognosis in pancreatic adenocarcinoma (22) and non-small cell lung cancer (23).…”

Section: Introductionmentioning

confidence: 96%

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High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

Kevans

Foley

Tenniswood

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The role of clusterin in tumor growth and progression remains unclear. Overexpression of cytoplasmic clusterin has been studied in aggressive colon tumors; however, no correlation between clusterin expression and survival in colorectal cancer has been identified to date. We assessed levels of clusterin expression in a group of stage II colorectal cancer patients to assess its utility as a prognostic marker. The study included 251 patients with stage II colorectal cancer. Tissue microarrays were constructed and immunohistochemistry done and correlated with clinical features and long term outcome. Dual immunofluorescence and confocal microscopy were used with terminal deoxynucleotidyltransferase -mediated dUTP nick-end labeling probes and clusterin antibody to assess the degree of co localization. Percentage epithelial cytoplasmic staining was higher in tumor compared with nonadjacent normal mucosa (P < 0.001). Within the stromal compartment, percentage cytoplamic staining and intensity was lower in tumor tissue compared with normal nonadjacent mucosa (P V 0.001). Survival was significantly associated with percentage epithelial cytoplasmic staining (P < 0.001), epithelial cytoplasmic staining intensity (P < 0.001), percentage stromal cytoplasmic staining (P = 0.002), and stromal cytoplasmic staining intensity (P < 0.001). Clusterin levels are associated with poor survival in stage II colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(2):393 -9)

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Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 82%

Section: Introductionmentioning

confidence: 96%

High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

Kevans

Foley

Tenniswood

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Immunohistochemical staining. In cases diagnosed as having micrometastases according to real-time RT-PCR, despite the lack of positive findings on routine pathologic examinations, sections adjunct to the site of the original sections for H&E staining were cut from the original formalin-fixed, paraffin-embedded blocks, and examined to determine whether occult foci of prostate cancer cells were present by immunohistochemical staining with a monoclonal antibody against PSA (Dako, Carpinteria, CA) using standard immunohistochemical techniques as reported previously (16). After staining, the sections were counterstained with hematoxylin.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Detection of Micrometastases in Pelvic Lymph Nodes in Patients with Clinically Localized Prostate Cancer by Real-time Reverse Transcriptase-PCR

Miyake

Hara

Kurahashi

et al. 2007

Clinical Cancer Research

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Purpose: Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer. Experimental Design:The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR.We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the ''presence of micrometastasis.'' Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done. Results: Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61lymph nodes from 17 patients with pathologically negative lymph nodes.The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence^free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined. Conclusions: These findings suggest that f30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

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“…The prognostic and predictive [20] value of CLU has already been evaluated in various malignancies, but conflicting results have been reported [6][7][8][9][21][22][23][24]. Conflicting data on the levels of CLU in lung cancer have also been found.…”

Section: Discussionmentioning

confidence: 89%

“…Indeed, CLU has been found to be involved in various physiologic processes important for carcinogenesis and tumor growth, including apoptotic cell death, cell cycle regulation, DNA repair, tissue remodeling, lipid transportation, membrane recycling, and immune system regulation [3][4][5]. Several studies have examined the prognostic value of CLU in various malignancies, with conflicting results [6][7][8][9]. Only one study investigated the prognostic role of CLU in a heterogeneous series of resected NSCLC, and the results suggested that CLU expression could be a positive prognostic indicator for NSCLC [10].…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of clusterin in resected adenocarcinomas of the lung

et al. 2013

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a b s t r a c tRationale: Clusterin expression may change in various human malignancies, including lung cancer. Patients with resectable non-small cell lung cancer (NSCLC), including adenocarcinoma, have a poor prognosis, with a relapse rate of 30-50% within 5 years. Nuclear factor kB (Nf-kB) is an intracellular protein involved in the initiation and progression of several human cancers, including the lung. Objectives: We investigate the role of clusterin and Nf-kB expression in predicting the prognosis of patients with early-stage surgically resected adenocarcinoma of the lung. Findings: The level of clusterin gradually decreased from well-differentiated to poorly differentiated adenocarcinomas. Clusterin expression was significantly higher in patients with low-grade adenocarcinoma, in early-stage disease and in women. Clusterin expression was inversely related to relapse and survival in both univariate and multivariate analyses. Finally, we observed an inverse correlation between Nf-kB and clusterin. Conclusions: Clusterin expression represents an independent prognostic factor in surgically resected lung adenocarcinoma and was proven to be a useful biomarker for fewer relapses and longer survival in patients in the early stage of disease. The inverse correlation between Nf-kB and clusterin expression confirm the previously reported role of clusterin as potent down regulator of Nf-kB.

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Expression of the secreted form of clusterin protein in renal cell carcinoma as a predictor of disease extension

Cited by 61 publications

References 20 publications

High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

Quantitative Detection of Micrometastases in Pelvic Lymph Nodes in Patients with Clinically Localized Prostate Cancer by Real-time Reverse Transcriptase-PCR

Prognostic role of clusterin in resected adenocarcinomas of the lung

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