Prognostic Impact of Jab1, p16, p21, p62, Ki67 and Skp2 in Soft Tissue Sarcomas
Open Access
- 5 October 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (10), e47068
- https://doi.org/10.1371/journal.pone.0047068
Abstract
The 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. Tissue 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. In 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). Increased 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.This publication has 63 references indexed in Scilit:
- Phosphorylation by p38 Mitogen-Activated Protein Kinase Promotes Estrogen Receptor α Turnover and Functional Activity via the SCFSkp2 Proteasomal ComplexMolecular and Cellular Biology, 2012
- Skp2: A novel potential therapeutic target for prostate cancerBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2012
- The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewalBlood, 2011
- Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in SarcomagenesisCancer Research, 2011
- Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's Sarcoma Family of TumorsInternational Journal of Cancer, 2010
- Credentialing a Preclinical Mouse Model of Alveolar RhabdomyosarcomaCancer Research, 2009
- Defining the Cooperative Genetic Changes That Temporally Drive Alveolar RhabdomyosarcomaCancer Research, 2008
- Skp2 expression is associated with high risk and elevated Ki67 expression in gastrointestinal stromal tumoursBMC Cancer, 2008
- Skp2B Stimulates Mammary Gland Development by Inhibiting REA, the Repressor of the Estrogen ReceptorMolecular and Cellular Biology, 2007
- Tissue microarrays (TMAs) for high-throughput molecular pathology researchInternational Journal of Cancer, 2001