Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases) and a validation set (124 cases). The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05), BCL2 (HR = 0.57, p = 0.001), PRC1 (HR = 1.51, p = 0.001), MMP9 (HR = 1.11, p = 0.08), SERF1a (HR = 0.83, p = 0.007). These five genes were combined into a linear score (signature) weighted according to the coefficients of the Cox model, as: 0.125FGF18 − 0.560BCL2 + 0.409PRC1 + 0.104MMP9 − 0.188SERF1A (HR = 2.7, 95% CI = 1.9–4.0, p < 0.001). The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001). Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.

546 Background: The aim of this study was look for the "core-genes" of published Signatures in order to find a simpler one Methods: To select candidate genes we used data of NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) including 408 breast cancer cases. Raw intensity data of Affymetrix HU133A and HU133B arrays of the two datasets (GSE1456 and GSE3494) were preprocessed using R/Bioconductor and the supercomputer Michelangelo ( www.litbio.org ). The candidate genes were selected from the “70-gene signature” (van 't Veer, Nature 2002), the “21-gene recurrence score” (Paik, NEJM 2004), the “two-gene–ratio model” (Ma, Cancer Cell 2004) and the “15-gene Insuline Resistence” signature (Gennari , JCO, Vol 25, No 18S, 2007: 10597), for a total of 98 genes.The 20 mRNA more significantly related to DFS were evaluated by quantitative reverse transcriptase PCR on 261 consecutive breast cancer cases, from paraffin embedded sections, split into a training (n 137) and a validation set (n 124). Results: The signature was developed on the training set and a multivariate stepwise Cox analysis selected 5 genes independently associated with DFS: FGF18 (HR=1.13, p=0.05) , BCL2 (HR=0.57, p=0.001), PRC1 (HR=1.51, p=0.001), MMP9 (HR=1.11, p=0.08), SERF1a (HR=0.83, p=0.007). These 5 genes were combined into a linear score weighted according to the coefficients of the Cox model, (0.125 FGF18 - 0.560 BCL2 + 0.409 PRC1 + 0.104 MMP9 - 0.188 SERF1A). The linear score was highly associated with DFS (HR=2.7, 95%CI=1.9-4.0, p<0.001). The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, medium or high risk of relapse as defined on the training set. The score resulted highly associated with DFS also in the validation set (p<0.001). Conclusions: Overexpression of BCL2 and SERF1A are related to a higher probability of relapse; overexpression of FGF18, PRC1 and MMP9 to a higher probability of survival without recurrence. The signature has a good discriminating ability and a further clinical validation is planned.

High‐ and low‐grade cervical lesions were analyzed for the presence of polyomavirus (PYV) and human papillomavirus (HPV) sequences. In precancerous cervical lesions, the overall prevalence of PYV sequences was 44% (41/93). Specifically, among the PYV‐positive samples, 83% (34/41) tested positive for BK polyomavirus (BKV) sequences, whereas 17% (7/41) were positive for JC‐virus. None of the samples were positive for simian virus 40. The presence of BKV DNA in high‐grade squamous intraepithelial lesions was confirmed by in situ PCR. BKV sequences were detected more frequently in high‐grade squamous intraepithelial lesions, together with the genotype HPV‐16. The association of BKV with precancerous cervical lesions suggests that this polyomavirus participates with HPV‐16 in the cell transformation process. Alternatively, BKV might multiply better in HPV‐16‐positive cells from precancerous cervical lesions than in HPV‐16‐negative cells. J. Med. Virol. 83:1770–1776, 2011. © 2011 Wiley‐Liss, Inc.

Background: Three novel polyomaviruses have been recently discovered: KI, WU and MC polyomaviruses. Their role in human pathology is debated while tissue tropism and site of latency remain unknown.Objective: To test the hypothesis that KI, WU and MC polyomaviruses can infect human tonsils.Study design: Archival paraffin-embedded tonsils from 91 patients affected by different tonsil diseases were screened by polymerase chain reaction to detect viral DNA of KIV, WUV, MCV, BKV and JCV. Phylogenetic and evolutionary analysis of the identified polyomaviruses was carried out.Results: Of the 91 tested specimens, 11 contained KIV DNA (12%), 4 WUV DNA (4.4%). 5 BKV DNA (5.5%). MCV and JCV were not detected. Phylogenetic analysis showed that KIVs identified in tonsils fall into a clade distinct from that containing KIVs isolated from respiratory secretions, respiratory tissue and feces. Moreover, four positively selected sites (4.5% of t-Ag sites) were found under strong positive selection (omega = 11.4), with posterior probabilities above 0.99. All the sites were located in the N-terminal region of the small t antigen.Conclusions: The results suggest that the novel KI and WU polyomaviruses can infect human tonsils. Future studies are needed to define their role in tonsil diseases. (C) 2009 Elsevier B.V. All rights reserved.

Although rare, gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. We present our experience with the treatment of 8 patients affected by gastrointestinal stromal tumours of the ileum and colon. These cases were characterised by acute bleeding, intestinal obstruction or diffuse abdominal pain, and all of them underwent an emergency surgical treatment. We performed six partial resections of the ileum, one right hemicolectomy and one left hemicolectomy. Three patients died after surgical procedures for disease relapse, one died 10 years later due to other complications, and the others are still alive.

The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.