Cell-Free DNA Integrity Analysis in Urine Samples

Although the presence of circulating cell-free DNA in plasma or serum has been widely shown to be a suitable source of biomarkers for many types of ...

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has not been investigated as widely as invasive breast cancer. Thus, the search for biomarkers capable of identifying DCIS lesions that may recur or progress to invasive cancer is ongoing. Although conventional steroid hormone receptors, cell proliferation and other important tumor markers have been extensively studied in invasive tumors, little is known about the role played by androgen receptors (ARs), widely expressed in breast cancer, in DCIS.

Role of androgen and estrogen receptors as prognostic and potential predictive markers of ductal carcinoma in situ of the breast.

In 2012, the Reggio Emilia Breast Cancer Screening Program introduced digital mammography in all its facilities at the same time. The aim of this work is to analyze the impact of digital mammography introduction on the recall rate, detection rate, and positive predictive value. The program actively invites women aged 45-74 years. We included women screened in 2011, all of whom underwent film-screen mammography, and all women screened in 2012, all of whom underwent digital mammography. Double reading was used for all mammograms, with arbitration in the event of disagreement. A total of 42,240 women underwent screen-film mammography and 45,196 underwent digital mammography. The recall rate increased from 3.3 to 4.4% in the first year of digital mammography (relative recall adjusted by age and round 1.46, 95% CI = 1.37-1.56); the positivity rate for each individual reading, before arbitration, rose from 3 to 5.7%. The digital mammography recall rate decreased during 2012: after 12 months, it was similar to the recall rate with screen-film mammography. The detection rate was similar: 5.9/1000 and 5.2/1000 with screen-film and digital mammography, respectively (adjusted relative detection rate 0.95, 95% CI = 0.79-1.13). The relative detection rate for ductal carcinoma in situ remained the same. The introduction of digital mammography to our organized screening program had a negative impact on specificity, thereby increasing the recall rate. The effect was limited to the first 12 months after introduction and was attenuated by the double reading with arbitration. We did not observe any relevant effects on the detection rate.

Impact of the Introduction of Digital Mammography in an Organized Screening Program on the Recall and Detection Rate.

Multiple myeloma cell growth relies on intrinsic aggressiveness, due to a high karyotypic instability, or on the support from bone marrow (BM) niche.We and other groups have provided evidences that Notch signaling is related to tumor cell growth, pharmacological resistance, localization/recirculation in the BM and bone disease.This study indicates that high gene expression levels of Notch signaling members (JAG1, NOTCH2, HES5 and HES6) correlate with malignant progression or high-risk disease, and Notch signaling may participate in myeloma progression by increasing the BM levels of interleukin-6 (IL-6), a major player in myeloma cell growth and survival. Indeed, in vitro results, confirmed by correlation analysis on gene expression profiles of myeloma patients and immunohistochemical studies, demonstrated that Notch signaling controls IL-6 gene expression in those myeloma cells capable of IL-6 autonomous production as well as in surrounding BM stromal cells. In both cases Notch signaling activation may be triggered by myeloma cell-derived Jagged ligands. The evidence that Notch signaling positively controls IL-6 in the myeloma-associated BM makes this pathway a key mediator of tumor-directed reprogramming of the bone niche.This work strengthens the rationale for a novel Notch-directed therapy in multiple myeloma based on the inhibition of Jagged ligands.

Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche.

Amplification of human telomerase is known to be associated with cervical tumorigenesis, although its role in tumor progression of cervical lesions is still unclear. We aimed to evaluate the role of telomerase in predicting the evolution of cervical lesions.

Role of Telomerase in Cervical Lesions as Prognostic Marker: A Comparison Between Immunohistochemistry and Fluorescence In Situ Hybridization.

In lung cancer patients, the only available diagnostic material often comes from biopsy or from cytological samples obtained by fine needle aspiration (FNA). There is a lack of easily detectable cytomorphological features for rapid on-site evaluation (ROSE) to orient lung cancer diagnosis towards a specific tumor histotype. We studied the cytological features evaluated on site to define tumor histotype and to establish the number of specimens to be taken. Cytological specimens from 273 consecutive patients were analyzed with ROSE: bronchoscopy with transbronchial needle aspiration (TBNA) had been performed in 72 patients and with endobronchial ultrasound (EBUS)-TBNA in 201. Cytomorphological features were correlated with the final diagnosis and diagnostic accuracy was measured. Analysis of the different cytomorphological parameters showed that the best sensitivity and specificity were obtained for adenocarcinoma by combining the presence of nucleoli and small/medium cell clusters, and for squamous cell carcinoma by considering the presence of necrosis ≥50% and large cell clusters. For small cell carcinoma, the best diagnostic accuracy was obtained by combining moderate necrosis (<50%) and the presence of single cells. Overall accuracy ranged from 90% to 97%. We showed that it was possible to establish the histotype of the most frequent lung cancers during ROSE using only a few easily identifiable cytomorphological parameters. An accurate diagnosis during ROSE could help endoscopists to decide how many tumor samples must be taken, e.g.a higher number of samples is needed for the biomolecular characterization of adenocarcinoma, whereas one sample may be sufficient for squamous cell carcinoma.

Sara Ravaioli

Biosciences Laboratory

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Cell-Free DNA Integrity Analysis in Urine Samples

Sara Ravaioli

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Biosciences Laboratory

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Cell-Free DNA Integrity Analysis in Urine Samples

Biosciences Laboratory