Abstract

PurposeThe purpose of this study is to clarify the prognostic significance of expression of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas (STS). Optimised treatment of STS requires better identification of high risk patients who will benefit from adjuvant therapy. The prognostic significance of Jab1, p16, p21, p62, Ki67 and Skp2 in STS has not been sufficiently investigated.Experimental DesignTissue 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 Jab1, p16, p21, p62, Ki67 and Skp2.ResultsIn univariate analyses, high tumor expression of Ki67 (P = 0.007) and Skp2 (P = 0.050) correlated with shorter disease-specific survival (DSS). In subgroup analysis, a correlation between Skp2 and DSS was seen in patients with malignancy grade 1 or 2 (P = 0.027), tumor size >5 cm (P = 0.018), no radiotherapy given (P = 0.029) and no chemotherapy given (P = 0.017). No such relationship was apparent for Jab1, p16, p21 and p62; but p62 showed a positive correlation to malignancy grade (P = 0.019). Ki67 was strongly positively correlated to malignancy grade (P = 0.001). In multivariate analyses, Skp2 was an independent negative prognostic factor for DSS in women (P = 0.009) and in patients without administered chemotherapy or radiotherapy (P = 0.026).ConclusionsIncreased expression of Skp2 in patients with soft tissue sarcomas is an independent negative prognostic factor for disease-specific survival in women and in patients not administered chemotherapy or radiotherapy. Besides, further studies are warranted to explore if adjuvant chemotherapy or radiotherapy improve the poor prognosis of STS with high Skp2 expression.

Highlights

  • Soft tissue sarcomas (STS) are a heterogeneous and highly malignant group of tumors originating from mesenchymal lineage.Local recurrence is common (20%) and metastases occur in one third of patients [1]

  • Further studies are warranted to explore if adjuvant chemotherapy or radiotherapy improve the poor prognosis of STS with high S-phase kinase-associated protein 2 (Skp2) expression

  • The purpose of this study was to clarify the prognostic significance of Jun activation domain binding protein 1 (Jab1), p16, p21, p62, Ki67 and Skp2 expression in non-gastrointestinal stromal tumor STS

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Summary

Introduction

Soft tissue sarcomas (STS) are a heterogeneous and highly malignant group of tumors originating from mesenchymal lineage.Local recurrence is common (20%) and metastases occur in one third of patients [1]. Soft tissue sarcomas (STS) are a heterogeneous and highly malignant group of tumors originating from mesenchymal lineage. Prognostic markers in potentially curable STS should guide therapy after surgical resection. Neoadjuvant therapy is increasingly used and may improve prognosis in high-risk cases [2], but requires prognostic factors that can be evaluated preoperatively. Used prognostic factors mainly include clinicopathological variables such as tumor type, size, depth, malignancy grade, necrosis, vascular invasion, and growth pattern, which are combined into different prognostic systems [3,4,5,6,7,8,9]. The loss of cell cycle control is a critical step in the development of neoplasia. The cell cycle is a series of carefully coordinated and regulated steps that govern cellular proliferation. Cyclin-dependent kinases (CDK) phosphorylate the retinoblastoma (Rb) doi:10.1371/journal.pone.0047068.g001

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