CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.

Hyojun Park,Sang Yun Ha,Anthony W. I. Lo,Kwang Yeol Paik,Sung Joo Kim,Seung Eun Lee,Choon Hyuck David Kwon,Jae Berm Park,Jong Man Kim,Jae-Won Joh,Sanghoon Lee,Yoon-La Choi

doi:10.1371/journal.pone.0099452

Abstract

BackgroundThe absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD) and dedifferentiated (DD) liposarcomas.MethodsFrom 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR).ResultsThere were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05). Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7%) and MDM2 amplification in 46 cases (95.8%). WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041). High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54) was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012) and multivariate analyses (P = 0.020).ConclusionsLevel of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

Highlights

Liposarcomas are the most common type of soft tissue sarcoma accounting for approximately 20% of all soft tissue sarcomas [1,2]
It has been suggested that an absence of CDK4 amplification in WD and DD liposarcomas is associated with lower rate of recurrence and favorable prognosis [6]
Patient and Tumor Characteristics One hundred thirty-nine patients were surgically treated for liposarcoma at our center during the study period

Summary

Introduction

Liposarcomas are the most common type of soft tissue sarcoma accounting for approximately 20% of all soft tissue sarcomas [1,2]. Well-differentiated (WD) liposarcomas are characterized by atypical but relatively mature adipocyte proliferation, while dedifferentiated (DD) liposarcomas consist of non-lipogenic spindle or pleomorphic cells with elevated mitotic activity [3,4]. These two histologic subtypes share a common genetic feature characterized by a supernumerary circular and/or giant rod chromosome containing a highly amplified sequence of genes from the 12q13-q21 region [5]. It has been suggested that an absence of CDK4 amplification in WD and DD liposarcomas is associated with lower rate of recurrence and favorable prognosis [6]. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD) and dedifferentiated (DD) liposarcomas

Objectives

Methods

Results

Conclusion