Prognostic Impact of Jab1, p16, p21, p62, Ki67 and Skp2 in Soft Tissue Sarcomas

Sørbye, Sveinung Wergeland; Kilvaer, Thomas K.; Valkov, Andrey Yurjevich; Dønnem, Tom; Smeland, Eivind; Al-Shibli, Khalid; Bremnes, Roy M.; Busund, Lill-Tove

doi:10.1371/journal.pone.0047068

Cited by 39 publications

(27 citation statements)

References 60 publications

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“…Oliveira found that Skp2 expression is associated with cell proliferation and a worse prognosis in 182 soft tissue sarcomas [5]. In a previous study we showed that high expression of Skp2 was a negative prognostic factor for DSS [6]. Interestingly, this correlation was statistically significant in females only, not in males.…”

Section: Introductionmentioning

confidence: 74%

Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

et al. 2013

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BackgroundS-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins. The purpose of this study is to clarify the prognostic significance of expression of Skp2 related to gender, estrogen receptor (ER) and progesterone receptor (PGR) in soft tissue sarcomas (STS). Skp2 has been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers. Optimized treatment of STS requires better identification of high-risk patients who will benefit from adjuvant therapy. The prognostic significance of Skp2 related to ER and PGR in STS has not been sufficiently investigated.MethodsTissue microarrays from 193 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of Skp2, ER and PGR.ResultsIn univariate analyses, high tumor expression of Skp2 correlated (p = 0.050) with reduced disease-specific survival (DSS). In subgroup analyses expression of PGR in males (p = 0.010) and in patients older than 60 years (p = 0.043) were negative prognostic factors for DSS. Expression of ER in females was a positive prognostic factor for DSS (p = 0.041). In co-expression analyses in the whole cohort, low expression of Skp2 in combination with low expression of ER was positive for DSS (p = 0.049). In females high expression of Skp2 in combination with low expression of ER was a negative prognosticator (p = 0.021). In the multivariate analyses, age (p = 0.012), malignancy grade (p < 0.001), wide resection margins (P = 0.010), ER negative / PGR positive co-expression profile (p = 0.002) and ER positive / PGR negative co-expression profile (p = 0.015) were independent negative prognostic factors for DSS. In females expression of Skp2 (p = 0.006) was associated with shorter DSS.ConclusionsWe found diverse prognostic impacts of expression of Skp2, ER, PGR and DSS in male and female patients with STS. In men, but not women, ER positive / PGR negative co-expression profile was an independent negative prognostic factor for DSS. In women, but not men, high expression of Skp2 was associated with reduced DSS.

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Section: Introductionmentioning

confidence: 74%

Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

et al. 2013

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“…The prognostic value of Ki-67 protein has been investigated in a number of studies with its potential as a reliable marker having been shown in cancers of the breast, soft tissue, lung, prostate, cervix and central nervous system (Sorbye et al, 2012;Josefsson et al, 2012;Ishihara et al, 2013). It has been shown that blocking of Ki-67 protein either by microinjection of antibodies leads to inhibit the progression of the cell cycle (Li et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Ki-67 Prognostic Value in Different Histological Grades of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Takkem

Barakat

Zakaraia

et al. 2018

Asian Pac J Cancer Prev

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Introduction:Abnormal cell proliferation appears to be a possible predictor of tumorigenesis, Ki-67 protein expression is closely related to the cell proliferation and could be used as a biomarker for the growth in the most of human tumors. The aim of the study: Investigating of Ki-67 expression in the pathological grades of oral epithelial dysplasia and oral squamous cell carcinomas.Materials and Methods:The sample consisted of 30 formalin-fixed, paraffin-embedded specimens of oral epithelial dysplasia (OED), 30 other of oral squamous cell carcinomas (OSCC), and 10 normal oral epithelium (NOE) were conventionally stained with hematoxylin and eosin and immunohistochemically stained with Ki-67 monoclonal antibody.Results:Expression of Ki-67 was restricted to the basal layers in the normal oral epithelium whereas Ki-67 positive cells in oral epithelial dysplasia (OED) were located in the basal, suprabasal and spinous layers, Ki-67 expression was increased in high-risk cases. Ki-67 positive cells in well-differentiated (OSCC) were located mainly in the periphery of the tumor nests, in moderately-differentiated (OSCC) were located in both peripheral and part of a center of the tumor nests whereas it was diffused in most of the Poorly-differentiated (OSCC). Statistical analysis indicated a significant difference between the expression in (OED) and (NOE), (OSCC) and (NOE), and no differences between (OED) and (OSCC).Conclusion:This study has concluded that Ki-67 antigen could be used as a marker for the histological grading of OED and OSCC, Expression of Ki 67 increased according to the severity of oral epithelial dysplasia.

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“…Local recurrence is common (20%), and metastases occur in one-third of the patients 1 2. Prognostic and predictive markers in potentially curable STS should guide therapy after surgical resection.…”

Section: Introductionmentioning

confidence: 99%

Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier

et al. 2014

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Aims p16(INK4a) is an important factor in carcinogenesis, and its expression is linked to oncogeneinduced senescence. Very recently it was shown that upregulation and downregulation of p16 indicates a senescence barrier in the serrated route of colorectal cancer. However, in soft tissue sarcoma (STS), the senescence mechanism is still not understood. In this study, we analysed a well characterised cohort of STS for p16(INK4a) expression and correlated the results with clinicopathological parameters including survival. Methods Tissue microarrays (TMA) of 183 soft tissue and bone tumours were analysed immunohistochemically. Furthermore, mRNA expression of p16(INK4a) was evaluated in four sarcoma cell lines, and a demethylation test was performed by treatment with 5-aza-2 0 -deoxycytide. Results On protein level, expression of p16(INK4a) was observed in undifferentiated pleomorphic sarcoma (UPS) in 69.1%, leiomyosarcoma in 85.7%, synovial sarcoma in 77.8%, liposarcoma in 88.9%, angiosarcoma in 60.9% and MPNST in 22.2%. Loss of p16(INK4a) was observed in high grade sarcomas and showed a significant correlation with reduced patient survival ( p=0.032). On DNA level, one out of four sarcoma cell lines exhibited a methylated p16(INK4a) promoter analysed by methylation-specific PCR. p16(INK4a) mRNA and protein expression was restored after demethylation using 5-aza-2 0 -deoxycytide. Conclusions Upregulation of p16(INK4a) might be associated with the induction of senescence and indicates a senescence barrier. Downregulation of p16(INK4a) is found in malignant progression, and is significantly correlated with reduced patient survival. Downregulation of p16(INK4a) may be explained by DNAhypermethylation in sarcoma cells.

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Prognostic Impact of Jab1, p16, p21, p62, Ki67 and Skp2 in Soft Tissue Sarcomas

Cited by 39 publications

References 60 publications

Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

Ki-67 Prognostic Value in Different Histological Grades of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier

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