Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study

Ghanim, Bahil; Klikovits, Thomas; Hoda, Mir Alireza; Láng, György; Szirtes, Ildikó; Setinek, Ulrike; Rózsás, Anita; Rényi-Vámos, F; László, Viktória; Grusch, Michael; Filipits, Martin; Scheed, A.; Jakopović, Marko; Samaržija, Miroslav; Brčić, Luka; Stančić-Rokotov, Dinko; Kern, Izidor; Rozman, Aleš; Dekan, Gerhard; Klepetko, Walter; Berger, Walter; Glasz, Tibor; Döme, Balázs; Hegedűs, Balázs

doi:10.1038/bjc.2015.9

Cited by 39 publications

(62 citation statements)

References 32 publications

(66 reference statements)

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“…We demonstrated that STMN1 was differentially expressed in normal, CIS, IC HSCC tissues. Elevated STMN1 was significantly associated with tumor differentiation, tumor size, clinical stage, lymph node metastasis and showed a positive correlation with Ki-67 index (19). Patients with moderate/strong STMN1 staining intensity always underwent poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new promoter in FaDu cell proliferation and migration

Chen

Zhang

Ding

et al. 2016

International Journal of Oncology

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Stathmin1, a microtubule-destabilizing phosphoprotein, is considered to play a crucial role in regulating cellular microtubule dynamics and controlling mitosis. Previous studies have showed that STMN1 is highly expressed in many human malignancies and is related to development, invasion and metastasis of tumors. However, its expression pattern, clinical performance and functional roles in hypopharyngeal squamous cell carcinoma (HSCC) have not been addressed. In this study, we found that STMN1 was significantly elevated in HSCC and its expression level was correlated with poor differentiation (P<0.001), clinical stage (P<0.001), large tumor size (P=0.001) and lymph node metastasis (P=0.008). A positive correlation between STMN1 and Ki-67 expression was also exhibited. High STMN1 expression predicted poor survival. Furthermore, we found that knockdown of STMN1 by siRNAs inhibited the FaDu cell proliferation and migration. Moreover, decreased STMN1 expression in FaDu cells reversed the acquisition of EMT phenotype by upregulating E-cadherin, as well as reduced vimentin expression at protein and mRNA levels. These results suggested that STMN1 plays an important role in proliferation and migration of HSCC and may be used as a potential prognostic biomarker or therapeutic target of HSCC.

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Section: Discussionmentioning

confidence: 99%

Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new promoter in FaDu cell proliferation and migration

Chen

Zhang

Ding

et al. 2016

International Journal of Oncology

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“…Further, MIB-1 acts as a monoclonal antibody which increases against Ki-67. In recent years, Ki-67 has been studied in many cancers, including cervical cancer,9 lung cancer,10 breast cancer11 and thyroid cancer 12. It has been reported that Ki-67 is an independent prognostic factor in thyroid cancer patients 13.…”

Section: Introductionmentioning

confidence: 99%

The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer: a meta-analysis with 6,051 cases

Pan¹,

Wen²,

Luo³

et al. 2017

OTT

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BackgroundGrowing evidence has demonstrated that Ki-67/MIB-1 has an effect on the clinical progression and prognosis in cancers. However, the diagnostic and prognostic values of Ki-67/MIB-1 in thyroid cancer remain unclear.Materials and methodsThe meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were retrieved from PubMed, EBSCO, EMBASE, ISI Web of Science, China National Knowledge Infrastructure, WanFang and Chinese VIP databases. MetaDiSc and STATA12.0 were used to analyze the meta-analysis. Fixed-effect analysis and random-effect analysis were applied to pool the relative ratio based on heterogeneity in this meta-analysis.ResultsIn the meta-analysis, 51 eligible studies were included. The pooled sensitivity of Ki-67/MIB-1 was 0.61 (95% confidence interval [CI]: 0.59–0.63) and specificity was 0.75 (95% CI: 0.74–0.77) in thyroid cancer. The pooled positive likelihood ratio was 3.19 (95% CI: 2.30–4.42) and negative likelihood ratio was 0.43 (95% CI: 0.35–0.54). In the diagnosis of thyroid cancer, the pooled diagnostic odds ratio of Ki-67/MIB-1 was 8.54 (95% CI: 5.03–14.49). The area under the symmetric receiver operating characteristic curve was 0.804 (standard error =0.031). Our results showed that there were statistical associations between Ki-67/MIB-1 and age (odds ratio [OR] =1.71, 95% CI: 1.14–2.57, P=0.010), tumor size (OR =1.86, 95% CI: 1.17–2.96, P=0.008), lymph node metastasis (OR =2.49, 95% CI: 1.42–4.39, P=0.002), metastasis status (OR =6.96, 95% CI: 2.46–19.69, P<0.001), tumor node metastasis stage (OR =6.56, 95% CI: 3.80–11.34, P<0.001) and extrathyroid extension (OR =1.91, 95% CI: 1.27–2.87, P=0.002). Furthermore, thyroid cancer patients with a high level of Ki-67/MIB-1 had a worse disease-free survival as compared to patients with a low level of Ki-67/MIB-1 (hazard ratio =5.19, 95% CI: 3.18–8.46, P<0.001). Also, Ki-67/MIB-1 was found to be associated with increased risk of mortality (hazard ratio =3.56, 95% CI: 1.17–10.83, P=0.025).ConclusionOur results demonstrated that Ki-67/MIB-1 might act as a potential factor in diagnosing thyroid cancer in Chinese. Also, the meta-analysis indicated that Ki-67/MIB-1 might have an effect on prognosis in non-Chinese thyroid cancer patients.

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“…In particular Ki67 proved to be an independent prognostic factor in epithelioid but not in non-epithelioid MPM (72). Interestingly ki67 index was lower in patients who received the induction chemotherapy (n=33, mean Ki67 index: 10.5±8.5) as compared to patients who had not received chemotherapy before sample collection (n=124, mean Ki67 index: 18.3±13.9, P<0.001), giving evidence of decrease of the MPM proliferative capacity after induction chemotherapy (72). Ki67 may be also a promising molecular candidate for the diagnosis of MPM: used in combination with repp86 (also called TPX2, Microtubule Nucleation Factor) showed a significant ability in differentiating MPM from benign reactive mesothelial hyperplasia (73).…”

Section: Clinical Implications Of Overexpressed Genes In Mpmmentioning

confidence: 87%

“…Recently it has been reported that patients with high Ki67 expression had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months) (72). In particular Ki67 proved to be an independent prognostic factor in epithelioid but not in non-epithelioid MPM (72). Interestingly ki67 index was lower in patients who received the induction chemotherapy (n=33, mean Ki67 index: 10.5±8.5) as compared to patients who had not received chemotherapy before sample collection (n=124, mean Ki67 index: 18.3±13.9, P<0.001), giving evidence of decrease of the MPM proliferative capacity after induction chemotherapy (72).…”

Section: Clinical Implications Of Overexpressed Genes In Mpmmentioning

confidence: 99%

“…The prognostic value of Ki67 in mesothelioma is known since 1998 when it has been reported a statistically significant difference between the survival of patients having a low and high Ki67 index (P<0.001) (106); subsequently other studies confirmed its prognostic significance (70,71). Recently it has been reported that patients with high Ki67 expression had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months) (72). In particular Ki67 proved to be an independent prognostic factor in epithelioid but not in non-epithelioid MPM (72).…”

Section: Clinical Implications Of Overexpressed Genes In Mpmmentioning

confidence: 99%

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Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

2018

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Malignant pleural mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. MPM patients have a very poor prognosis with a median survival of less than one year from the onset of symptoms. The biomarkers proposed so far do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the finding of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. Gene overexpression has been frequently associated with a malignant phenotype in several cancer types; therefore the identification of overexpressed genes may lead to the detection of novel prognostic or diagnostic marker and to the development of novel therapeutic approaches, based on their inhibition. In the last years, several overexpressed genes have been identified in MPM through gene expression profiling techniques: among them it has been found a group of 51 genes that resulted overexpressed in more than one independent study, revealing their consistency among studies. This article reviews the clinical implications of confirmed overexpressed genes in MPM described so far in literature.

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Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study

Cited by 39 publications

References 32 publications

Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new promoter in FaDu cell proliferation and migration

Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new promoter in FaDu cell proliferation and migration

The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer: a meta-analysis with 6,051 cases

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

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