Abstract 1780: p53 mutation predicts limited benefit from adjuvant chemotherapy in patients with localized completely resected high grade soft tissue sarcoma: a retrospective study on 117 patients of the French Sarcoma Group
Authors: Blay Jean-Yves , de The Hughes , Italiano Antoine , Bui Binh , Ranchere Dominique , Perrier Philippe , Cesne Axel Le , Leroux Agnès , Collin Francoise , Coindre Jean Michel 
Published: February 2011

Rationale

TP 53 is frequently mutated in some sarcoma subtypes and its mutation status has been reported to be correlated to survival in some studies. We investigated whether TP53 status may play a role in determining outcome following resection of the primary tumor.

Material and methods

The functional status of p53 was tested in a retrospective series of 117 patients of the French Sarcoma Group with localized grade 2or 3 STS treated with surgery, followed by radiotherapy (70) and/or chemotherapy (37%) in whom frozen pre-treatment material was available. FASAY (Functional Analysis of Separated Alleles in Yeast) was used to test the functional properties of p53. Statistical analysis were performed using SPSS 16.0.

Results

The diagnosis and primary surgery was performed between April 1990 and March 2006. Median follow up was 10,5 years. There were 62% males 38% females, aged 16 to 92 (median 64) with 74% primary locations of the limbs, 26 trunk or H&N respectively. Major histotypes were MFH/undifferentiated (32%) leiomyosarcomas (LMS, 27%), liposarcomas (LPS, 16%), while grade 2 and 3 represented 27% and 73% respectively Functional inactivation of p53 was observed in 31 tumors (29%), and was not correlated to age, gender, site, histotype, with the exception of dedifferentiated LPS which never expressed a no functional p53 (0/12 vs 31/100, p=0.01). Mutations were more frequently observed in grade 3 vs grade 2 (33% vs 13%, p=0.03). 70% patients received adjuvant radiotherapy, and 17% received adjuvant chemotherapy (AdjCT). Adjuvant RT was not correlated to RFS and OS. Adjuvant CT was associated with a better RFS (trend p=0.07) and a better OS (p=0.008). P53 mutation was correlated marginally to a worse OS (p=0.03), and a worse RFS (p=0.03) in univariate analysis. Similar results were obtained when the DDLPS subgroup of patients- with mdm2 amplification, was removed from the group (p=0.01 and 0.006 for RFS and OS). Using Cox model with gender, age, size, LPS histology, depth, R, grade, trunk sites, p53, adjCT), only the last three were independently correlated to OS, while size, p53, and adjCT were retained by the model for RFS. In the WT p53 group, adjCT improved RFS (trend p=0,07) and OS (p=0,007). RT improved significantly RFS (p=0.001) and marginally OS (0.06). In Cox model in the WT group, tumor size, adjCT for RFS, and gender, DDLPS and adjCT for OS were the only independent factors Conversely, in the MUT p53 group, OS and RFS were super-imposable with adjuvant CT and adjuvant RT trending towards a worse outcome in the CT+ and RT+ subgroups.

Conclusion:

Mutations of p53 using Fasay correlated to RFS and OS and to a limited or no benefit of adjuvant CT for RFS and OS. A prospective series is required to confirm this observation which may be helpful for patient selection in the future.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1780.