TY - JOUR
T1 - Skp2 overexpression is highly representative of intrinsic biological aggressiveness and independently associated with poor prognosis in primary localized myxofibrosarcomas
AU - Huang, Hsuan Ying
AU - Kang, Hong Yo
AU - Li, Chien Feng
AU - Eng, Hock Liew
AU - Chou, Shih Cheng
AU - Lin, Ching Nan
AU - Hsiung, Ching Yeh
PY - 2006/1/15
Y1 - 2006/1/15
N2 - Purpose: Two SCFSkp2 ubiquitin ligase - related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in posttranscriptional degradation of p27Kip1 tumor suppressor. We analyzed the prognostic utility of p27Kip1 and its interacting cell cycle regulators in myxofibrosarcomas. Experimental Design: Clinicopathologic features and tissue microarray - based immunohistochemical expression of p27Kip1, Skp2, Cks1, cyclin E, cyclin A, Ki-67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and the relationship between Skp2 and p27Kip1 proteins were examined in six cases by semiquantitative reverse transcription-PCR and Western blotting, respectively. Results: High indices of Skp2 (≥10%), cyclin A (≥10%), and Mcm2 (≥50%) were adverse prognosticators at the univariate level. Furthermore, co-overexpression of Skp2 and cyclin A identified highly lethal cases in the entire cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall survivat (OS)] and the lower-grade subset (Fédération Nationale des Centres de Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In multivariate analyses, Skp2 overexpression overshadowed most intrinsic clinicopathologic factors and independently correlated with worse metastasis-free survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive margins independently predicted inferior local recurrence-free survival (P = 0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation of Skp2 mRNA in four cases and Western blotting displayed a matched expression pattern of Skp2. Conclusions: Margin status and intrinsic property of myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly representative of the biological aggressiveness of myxofibrosarcomas and plays an important prognostic role.
AB - Purpose: Two SCFSkp2 ubiquitin ligase - related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in posttranscriptional degradation of p27Kip1 tumor suppressor. We analyzed the prognostic utility of p27Kip1 and its interacting cell cycle regulators in myxofibrosarcomas. Experimental Design: Clinicopathologic features and tissue microarray - based immunohistochemical expression of p27Kip1, Skp2, Cks1, cyclin E, cyclin A, Ki-67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and the relationship between Skp2 and p27Kip1 proteins were examined in six cases by semiquantitative reverse transcription-PCR and Western blotting, respectively. Results: High indices of Skp2 (≥10%), cyclin A (≥10%), and Mcm2 (≥50%) were adverse prognosticators at the univariate level. Furthermore, co-overexpression of Skp2 and cyclin A identified highly lethal cases in the entire cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall survivat (OS)] and the lower-grade subset (Fédération Nationale des Centres de Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In multivariate analyses, Skp2 overexpression overshadowed most intrinsic clinicopathologic factors and independently correlated with worse metastasis-free survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive margins independently predicted inferior local recurrence-free survival (P = 0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation of Skp2 mRNA in four cases and Western blotting displayed a matched expression pattern of Skp2. Conclusions: Margin status and intrinsic property of myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly representative of the biological aggressiveness of myxofibrosarcomas and plays an important prognostic role.
UR - http://www.scopus.com/inward/record.url?scp=31544465982&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-1497
DO - 10.1158/1078-0432.CCR-05-1497
M3 - 文章
C2 - 16428491
AN - SCOPUS:31544465982
SN - 1078-0432
VL - 12
SP - 487
EP - 498
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -
