Localised angiosarcomas: the identification of prognostic factors and analysis of treatment impact. A retrospective analysis from the French Sarcoma Group (GSF/GETO).

BACKGROUND: Angiosarcomas represent less than 2% of all adult soft tissue sarcomas. Prognostic factors and the role of (neo-) adjuvant treatments in the management of localised angiosarcomas require further investigation. METHODS: We have conducted a retrospective multicenter study (June 1980 to October 2009) of 107 patients with localised angiosarcomas. All of the cases were centrally reviewed by a certified pathologist. Univariate and multivariate analyses were conducted to identify independent poor prognostic factors (PF). Overall survival (OS) and Local Recurrence-Free Survival (LRFS) were estimated using the Kaplan-Meier method. The effect of treatments was explored using the Cox model after adjusting for the PF. RESULTS: The median age was 71 years. 22.4% and 62.6% developed an angiosarcoma in pre-existing lymphoedema and within irradiated tissue respectively. The median OS, LRFS and Disease Recurrence-Free Survival (DRFS) were 38.8, 27 and 36.1 months, respectively. In multivariate analysis, the following parameters influenced the OS: lymphoedema (Hazard ratio (HR)=2.0) and size >5cm (HR=1.5). After adjustment to these PF, R0 margins was the only treatment parameter that improving the OS (HR=0.2). In the multivariate analysis, the LRFS was influenced by an age >70 (HR=1.8) and pre-existing lymphoedema (HR=2.0). After adjustment for these PF, R0 margins (HR=0.5) and adjuvant radiotherapy (HR=0.3) improved the LRFS. CONCLUSIONS: Our results suggest the following points: (i) pre-existing lymphoedema, tumour size and age >70 are probably the major prognostic factors in patients with localised angiosarcomas; (ii) the achievement of R0 margins is probably of major importance for improving the patient outcome and (iii) adjuvant radiotherapy probably decreased the risk of local recurrence.

Relationships between progesterone receptor isoforms and the HER/ErbB receptors and ligands network in 299 primary breast cancers.

BACKGROUND: The effects of progesterone are mediated by 2 progesterone receptors (PR), PR-A and PR-B. Recently, several lines of evidence have suggested that reduced PR expression may result from hyperactivity in the signaling cascade generated by the HER/ErbB family. The aim of this study was to analyze the relationships between PR isoforms and the network of the HER/ErbB receptors and ligands in breast cancer. PATIENTS AND METHODS: 299 breast cancer samples from patients operated in our institute for locoregional disease between May 1989 and December 1991 were included. The mRNA expression of total PR-A+B isoforms and PR-B isoform were quantified by real time quantitative RT-PCR using TaqMan® probes. RESULTS: mRNA levels of the PR isoforms positively correlated with protein levels of estradiol receptors (ER) and PR. The PR isoforms mRNA levels were inversely correlated with clinicopathological markers of tumor aggressiveness, such as SBR grading and lymph node involvement. The PR isoforms positively correlated with the mRNA levels of HER/ErbB receptors and ligands associated with a more differentiated phenotype (HER3, HER4, EGF, AREG, NRG3 and NRG4) while they correlated negatively with those associated with aggressiveness (EGFR, TGFa, HB-EGF, EREG, and NRG2). CONCLUSION: Our results demonstrate the existence of strong correlations between mRNA levels of the PR isoforms, protein levels of hormone receptors, HER/ErbB receptors and ligands network, and thus suggest that crosstalks between PR and the HER family are a hallmark of breast cancer growth.