Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

<p>Abstract</p> <p>Background</p> <p>Several studies demonstrated that epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC) and to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (CRC). In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic <it>in situ </it>hybridization (CISH) is an alternative technique to fluorescence <it>in situ </it>hybridization (FISH), but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC) of lung nodules has not yet been established.</p> <p>Methods</p> <p>We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas) and 13 lung metastases from CRC.</p> <p>Results</p> <p>Of the 33 FNAC analyzed by CISH, 27 (82%) presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30%) showed a low polysomy, 15 (45%) a high polysomy and 2 (6%) NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p < 0.0001). Two cases were amplified with both assays, whereas 1 case of NSCLC was amplified by FISH only. CISH sensitivity was 67%, the specificity and positive predictive value (PPV) was 100%, and the negative predictive value (NPV) was 97%.</p> <p>Conclusions</p> <p>Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.</p

Role of WB-MR/DWIBS compared to 18F-FDG PET/CT in the therapy response assessment of lymphoma

Introduction: This study prospectively evaluated whole-body magnetic resonance/diffusion-weighted imaging with body signal suppression (WB-MR/DWIBS) reliability compared to 18F-FDG PET/CT in the treatment response assessment of classic Hodgkin lymphomas (HL) and aggressive non-Hodgkin lymphomas (aNHL). Materials and methods: Twenty-seven consecutive patients were prospectively enrolled at the time of diagnosis. Eighteen (11 HL and seven aNHL) were considered for the analysis. They received chemo/radiotherapy as induction and completed post-treatment evaluation performing both 18F-FDG PET/CT and WB-MR/DWIBS. The revised response criteria for malignant lymphomas were used to assess the response to treatment. We evaluated the agreement between the two methods by Cohen’s K test. Post-therapy WB-MR/DWIBS sensitivity, specificity, PPV, NPV and accuracy were then calculated, considering the 12 months of follow-up period as the gold standard. Results: By using an evaluation on a lesion-by-lesion basis, WB-MR/DWIBS and 18F-FDG PET/CT showed an overall good agreement (K = 0.796, 95 % IC = 0.651–0.941), especially in the evaluation of the nodal basins in aNHL (K = 0.937, 95 % IC = 0.814–1). In reference to the revised response criteria for malignant lymphomas, the two methods showed a good agreement (K = 0.824, 95 % IC = 0.493–1). Post-therapy sensitivity, specificity, PPV, NPV and accuracy of WB-MR/DWIBS were 43, 91, 75, 71 and 72 %, respectively. Conclusion: WB-MR/DWIBS seems to be an appropriate method for the post-treatment assessment of patients affected by HL and aNHL. The small discrepancies between the two methods found within HL could be due to the biological and metabolic behavior of this group of diseases. Larger prospective studies are necessary to better define the role of WB-MR/DWIBS in this setting of patients

Role of Cardiovascular Magnetic Resonance in Cardiac Amyloidosis: A Narrative Review

: Amyloidosis is a rare infiltrative condition resulting from the extracellular accumulation of amyloid fibrils at the cardiac level. It can be an acquired condition or due to genetic mutations. With the progression of imaging technologies, a non-invasive diagnosis was proposed. In this study, we discuss the role of CMR in cardiac amyloidosis, focusing on the two most common subtypes (AL and ATTR), waiting for evidence-based guidelines to be published

Prioritization of putatively detrimental variants in euploid miscarriages

none17Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed GP , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.noneBuonaiuto, Silvia; Biase, Immacolata Di; Aleotti, Valentina; Ravaei, Amin; Marino, Adriano De; Damaggio, Gianluca; Chierici, Marco; Pulijala, Madhuri; D’Ambrosio, Palmira; Esposito, Gabriella; Ayub, Qasim; Furlanello, Cesare; Greco, Pantaleo; Capalbo, Antonio; Rubini, Michele; Biase, Sebastiano Di; Colonna, VincenzaBuonaiuto, Silvia; Biase, Immacolata Di; Aleotti, Valentina; Ravaei, Amin; Marino, Adriano De; Damaggio, Gianluca; Chierici, Marco; Pulijala, Madhuri; D’Ambrosio, Palmira; Esposito, Gabriella; Ayub, Qasim; Furlanello, Cesare; Greco, Pantaleo; Capalbo, Antonio; Rubini, Michele; Biase, Sebastiano Di; Colonna, Vincenz

Prioritization of putatively detrimental variants in euploid miscarriages

Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed gp , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages