Prognostic factors in early-stage leiomyosarcoma of the uterus.

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

Strong smooth muscle differentiation is dependent on myocardin gene amplification in most human retroperitoneal leiomyosarcomas.

Myocardin (MYOCD), a serum response factor (SRF) transcriptional cofactor, is essential for cardiac and smooth muscle development and differentiation. We show here by array-based comparative genomic hybridization, fluorescence in situ hybridization, and expression analysis approaches that MYOCD gene is highly amplified and overexpressed in human retroperitoneal leiomyosarcomas (LMS), a very aggressive well-differentiated tumor. MYOCD inactivation by shRNA in a human LMS cell line with MYOCD locus amplification leads to a dramatic decrease of smooth muscle differentiation and strongly reduces cell migration. Moreover, forced MYOCD expression in three undifferentiated sarcoma cell lines and in one liposarcoma cell line confers a strong smooth muscle differentiation phenotype and increased migration abilities. Collectively, these results show that human retroperitoneal LMS differentiation is dependent on MYOCD amplification/overexpression, suggesting that in these well-differentiated LMS, differentiation could be a consequence of an acquired genomic alteration. In this hypothesis, these tumors would not necessarily derive from cells initially committed to smooth muscle differentiation. These data also provide new insights on the cellular origin of these sarcomas and on the complex connections between oncogenesis and differentiation in mesenchymal tumors.

A Variscan pressure-temperature-time path for the N-E Mont Blanc massif

The northeastern portion of the Mont Blanc massif in western Switzerland is predominantly comprised of the granitic rocks of the Mont Blanc intrusive suit, and the Mont Blanc basement gneisses. Within these metamorphic rocks are a variety of sub-economic Fe skarns. The mineral assemblages and fluid inclusions from these rocks have been used to derive age, pressure, temperature and fluid composition constraints for two Variscan events. Metamorphic hornblendes within the assemblages from the basement amphibolites and iron sk:lms have been dated using Ar-40/Ar-39, and indicate that these metamorphic events have a minimum age of approximately 334 Ma. Garnet-hornblende-plagioclase thermobarometry and stable isotope data obtained from the basement amphibolites are consistent with metamorphic temperatures in the range 515 to 580 degrees C, and pressures ranging from 5 to 8 kbar. Garnet-hornblende-magnetite thermobarometry and fluid inclusion studies indicate that the iron skarns formed at slightly lower temperatures, ranging from 400 to 500 degrees C in the presence of saline fluids at formational pressures similar to those experienced by the basement amphibolites. Late Paleozoic minimum uplift rates and geothermal gradients calculated using these data and the presence of Ladinien ichnofossils are on the order of 0.32 mm/year and 20 degrees C/km respectively. These uplift rates and geothermal gradients differ from those obtained from the neighbouring Aiguilles Rouges massif and indicate that these two massifs experienced different metamorphic conditions during the Carboniferous and Permian periods. During the early to late Carboniferous period the relative depths of the two massifs were reversed with the Aiguilles Rouges being initially unroofed at a much greater rate than the Mont Blanc, but experiencing relatively slower uplift rates near the termination of the Variscan orogeny.