Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

Özyalvaçlı, Gülzade; Özyalvaçlı, Mehmet Emin; Astarci, Hesna Muzeyyen; Boran, Çetin; Yesil, Cemile; Üyetürk, Uğur; Aktaş, Gülan

doi:10.5114/pjp.2015.51154

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…Bladder tumors with Ki-67 expression have aggressive behaviors, such as multifocality, concomitant CIS, and increased EORCT risk scores, in addition to higher grade/stage [ 14 , 15 ]. Because Ki-67 is a cellular proliferation marker, some studies claim that it is more closely related to the recurrence of NMIBC rather than progression to MIBC [ 14 , 16 ]. Other studies reported that Ki-67 was related not only to recurrence but also to progression and survival [ 15 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Disease-specific death was any death because of bladder cancer in patients with documented metastatic or recurrent disease. Compared with the primary tumor, progression was defined in individual studies as development of a higher stage [ 6 , 14 ]; development of a higher stage and/or grade [ 27 , 31 ]; development of a higher stage and/or grade as well as development of regional or distant metastases [ 25 ]; development of a higher stage or metastasis [ 10 , 16 , 17 , 33 , 36 , 37 , 41 ], or development of a higher stage and muscle invasive cancer (≥ T2), distant metastasis, or death from bladder cancer [ 11 ]. Additional definitions of progression included development of MIBC (≥ T2) [ 34 , 45 , 47 ] and development of MIBC (≥ T2) and/or metastasis [ 15 , 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

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Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Jeong

Kwak

et al. 2017

Oncotarget

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PurposeThis meta-analysis evaluated the prognostic significance of Ki-67 in non-muscle invasive bladder cancer (NMIBC).Materials and MethodsWe selected 39 articles including 5,229 patients from Embase, Scopus, and PubMed searches. The primary outcomes, recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were determined using time-to event hazard ratios (HRs) with 95% confidence intervals (CIs). Study heterogeneity was tested by chi-square and I2 statistics. Heterogeneity sources were identified by subgroup meta-regression analysis.ResultsTwo studies were prospective; 37 were retrospective. Immunohistochemistry was performed in tissue microarrays or serial sections. A wide range of antibody dilutions and Ki-67 positivity thresholds were used. Study heterogeneity was attributed to analysis results in studies of RFS (p < 0.0001). Meta-regression analysis revealed that region and analysis results accounted for heterogeneity in PFS studies (p = 0.00471, p < 0.0001). High Ki-67 expression was associated with poor RFS (pooled HR, 1.78; 95% CI, 1.48–2.15), poor PFS (pooled HR, 1.28; 95% CI, 1.13–2.15), poor DSS (pooled HR, 2.24; 95% CI, 1.47–2.15), and worse OS (pooled HR, 2.29; 95% CI, 1.24–4.22).ConclusionsThe meta-analysis found that current evidence supports the prognostic value of Ki-67 in NMIBC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Jeong

Kwak

et al. 2017

Oncotarget

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“…Microscopic examination of bladder tumours obtained during transurethral resection (TUR) is the most important diagnostic and staging tool, and directly influences therapeutic decisions in patients with bladder cancer [1]. The examination should define the histological origin of the cancer, depth of cancer cell invasion, and grade of the cancer and describe the tumour configuration, provide information on whether a muscle layer is present in the specimen, as well as other information [2,3]. Despite improvements in surgical technique and histological methods, microscopic examinations of TUR specimens remain difficult.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical differentiation between muscularis mucosae and muscularis propria for improving the staging of bladder cancer in patients undergoing transurethral resection of bladder tumours

Poletajew¹,

Wolińska²,

Wasiutyński³

et al. 2017

pjp

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Microscopic differentiation between muscularis mucosae (MM) and muscularis propria (MP) of the bladder in the material obtained during transurethral resection (TUR) remains difficult. The study was aimed at determination of the usefulness of immunohistochemical staining in this context. Forty-seven TUR specimens were stained with 5 mouse anti-human antibodies: anti-desmin, anti-filamin, anti-type IV collagen, anti-smoothelin, and anti-vimentin. Slides were assessed under light microscopy and the intensity of the immune reaction within MM and MP was evaluated on a four-level visual scale as follows: negative (0) and weakly (1), moderately (2), or strongly (3) positive. MM was identified in 27 patients (57.4%). The modal values of reaction intensity in MM and MP was 0 and 2 for desmin (p > 0.05), 2 and 2 for filamin (p = 0.01), 2 and 2 for type IV collagen (p > 0.05), 1 and 2 for smoothelin (p = 0.03), and 2 and 0 for vimentin (p = 0.02), respectively. Identical intensity within MM and MP was observed in 7.1%, 28.6%, 20%, 30.1%, 5.6%, respectively. Immunohistochemistry can help differentiate between MM and MP in TUR specimens. As of yet, no single marker can reliably differentiate between MM and MP; however, a combination of anti-filamin, anti-smoothelin, and anti-vimentin antibodies may be reasonable for diagnostic purposes.

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“…Overall, 3241 records, identified irrelevant by title and abstract screening, were excluded; and the remained 441 records, which investigated the relationship between Ki-67 reactivity and survival outcomes of BC patients, were evaluated in full text. According to our inclusion criteria, 76 studies (n = 13,053 patients), 9 , 13 – 15 , 26 – 96 published from 1997 to 2015, were eligible and eventually included in our meta-analysis for analysis of the correlation between Ki-67 reactivity and clinical prognosis of BC patients (Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

Luo

Zhang

et al. 2016

Medicine

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Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature.A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0.In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05).The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the me...

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Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

Cited by 6 publications

References 36 publications

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Immunohistochemical differentiation between muscularis mucosae and muscularis propria for improving the staging of bladder cancer in patients undergoing transurethral resection of bladder tumours

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

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