The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.

BACKGROUND: Digital ulcers (DU) affect 50% of systemic sclerosis (SSc) patients, representing a challenging clinical problem. Despite a high negative predictive value, capillaroscopic scores proposed to select patients at risk for DU show an inadequate positive predictive value, especially in patients without previous DU. AIM OF THIS STUDY: To increase the predictive value for DU development of capillaroscopy, through a predictive risk chart taking into account capillaroscopic, demographic, and clinico-serological parameters. PATIENTS AND METHODS: Two hundred and nineteen unselected SSc patients from 8 Italian Rheumatology Centers were consecutively enrolled during a 6-month period. Demographic, clinical, serological and instrumental data and capillaroscopy skin ulcers risk index (CSURI) were collected. A. Manfredi et al. / Prediction risk chart for scleroderma digital ulcers RESULTS:A multivariate logistic regression analysis showed a significant positive association between DU appearance and male gender, DU history, altered CSURI, and ESR. A prediction risk chart of the development of DU within 6 months were built on the basis of the above parameters. According to the risk level, four risk classes were identified: low (≤19.3%); medium (>19.3%, ≤58.6%); high (>58.6%, ≤89.2%), and very high risk (>89.2%). CONCLUSIONS: The systematic evaluation of the above parameters can be helpful to identify patients at risk to develop DU optimizing preventive vasoactive therapy.

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Breast cancer evolves thanks to a dense and close interaction with the surrounding tumor microenvironment (TME). Fibroblasts, leukocytes, blood and lymphatic endothelial cells and extracellular matrix are the constituents of this entity, and they synergistically play a pivotal role in all of the stages of breast cancer development, from its onset to its metastatic spread. Moreover, it has been widely demonstrated that variations to the TME can correspond to prognosis variations. Breast cancer not only modulates the transformation of the environment within the mammary gland, but the same process is observed in metastases as well. In this minireview, we describe the features of TME within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.

AIMThe BRAF mutation is a rare pathogenetic alternative to KIT/PDGFRA mutation in GIST and causes Imatinib resistance. A recent description of KIT and BRAF mutations co-occurring in an untreated GIST has challenged the concept of their being mutually exclusive and may account for ab initio resistance to Imatinib, even in the presence of Imatinib-sensitive KIT mutations. BRAF sequencing is generally limited to KIT/PDGFRA wild-type cases. Hence, the frequency of concomitant mutations may be underestimated.METHODSWe screened for KIT (exon 9, 11, 13, 17), PDGFRA (exon 12,14, 18) and BRAF (exon 15) mutations a series of 407 GIST. Additionally, we evaluated the BRAF V600E mutation-specific antibody, VE1, as a surrogate for V600E mutation, on a series of 313 GIST (24 on whole sections, 288 cases on tissue array), including 6 cases molecularly ascertained to carry the BRAF V600E mutation.RESULTSNo concomitant KIT/BRAF or PDGFRA/BRAF mutations were detected. BRAF mutation was detected only in one case, wild-type for KIT/PDGFRA. All the 6 BRAF-mutant cases stained positive with the VE1 antibody. A weak VE1 expression was observed in 14/287 (4.9%) BRAF wild-type cases, as observed also in 2/6 BRAF-mutant cases. Overall in our series, sensitivity and specificity of the VE1 antobody were 100% and 95.1%, respectively.CONCLUSIONThe concomitance of BRAF mutation with either KIT or PDGFRA mutation is rare in GIST. In these tumors, moderate/strong VE1 immunoreactivity is a valuable surrogate for molecular analysis. Instead, genotyping is warranted in the presence of weak VE1 staining.