Explore the vast range of titles available.

Background/Objectives: Mesenchymal–epithelial transition (MET) gene amplification is a critical biomarker in non-small cell lung cancer (NSCLC), significantly influencing treatment decisions and prognostic evaluations. However, current detection methods such as fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) have limitations in speed, cost, and specificity, particularly when distinguishing between focal MET amplification and MET polysomy. Methods: This study introduces a novel digital PCR (dPCR) assay designed not only to detect MET amplification but also to differentiate between its focal and non-focal subtypes. The assay was evaluated against established FISH and targeted NGS panels using 55 NSCLC samples with known MET amplification statuses (26 positive and 29 negative) confirmed by FISH and NGS. Results The dPCR assay demonstrated high sensitivity (96.0%) and specificity (96.7%), achieving 100% concordance with FISH in differentiating focal MET amplification from MET polysomy. Additionally, the assay exhibited excellent precision, accuracy, and linearity (R2 = 1.00) in MET copy number quantification, surpassing NGS in diagnostic performance. Offering a robust, cost-effective, and efficient alternative to FISH, the dPCR assay significantly reduces the turnaround time (3 h versus 2 days) and provides a quantitative and objective method for MET amplification detection and subtype differentiation. This makes it suitable for clinical laboratories with limited molecular expertise. Conclusions: This study highlights the potential of the dPCR assay to complement existing molecular diagnostic techniques, delivering reliable and actionable results for MET-targeted therapy selection in NSCLC patients and thereby advancing precision oncology.

The T790M mutation in the epidermal growth factor receptor gene causes most acquired resistance to firstor second-line epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small-cell lung cancer. The results of T790M testing can guide subsequent treatment. Despite the availability of guidelines from international organisations, T790M testing practices in Hong Kong must be streamlined and adapted to the Hospital Authority setting. To address this issue, a panel of experts in oncology and pathology met for discussion of key topics regarding T790M testing practices in Hong Kong, including the appropriate timing of testing and re-testing, as well as optimal testing methods. All panel members voted on the results of the discussion to achieve consensus. Items supported by a majority vote were adopted as consensus statements regarding current best practices for T790M testing in Hong Kong. Among the topics discussed, the panel agreed that T790M testing should be initiated upon radiological progression, including symptomatic disease progression or central nervous system-only progression. The experts also preferred initial testing with liquid biopsy, using the widely available digital polymerase chain reaction platform. This document provides the final consensus statements, as well as a testing and treatment workflow, for clinicians in Hong Kong to use as guidance in T790M testing.

To compare the PathVysion fluorescence in-situ hybridisation assay with the INFORM HER2 Dual in-situ hybridisation assay on 104 invasive breast cancers with a broad spectrum of immunohistochemistry scores. This case series involved consecutive patients diagnosed with invasive breast carcinoma with equivocal immunohistochemistry score and referred for further HER2 assessment from the departments of Surgery and/or Clinical Oncology of the two hospitals between January 2013 and February 2014. An additional 10 cases with negative HER2 immunohistochemistry and 11 cases with positive HER2 immunohistochemistry were further included. The results of both fluorescence in-situ hybridisation and dual in-situ hybridisation were available in 99 of 104 cases, respectively. Student’st test showed no statistically significant difference in the mean number of HER2 count, CEP17 copies, or HER2/CEP17 ratio between that obtained by fluorescence in-situ hybridisation and that obtained by dual in-situ hybridisation. Pearson’s correlation of results for the two assays was strong for HER2/CEP17 signal ratio (R=0.963, P<0.001) and mean HER2 copies per nucleus (R=0.897, P<0.001). Overall agreement was 96.0% (95 out of 99 cases, ĸ0.882). Three of the four discordant cases were equivocal for either fluorescence in-situ hybridisation or dual in-situ hybridisation. The results of immunohistochemistry 0/1+ and 3+ cases showed 100% concordance between the two assays. The failure rate was 0.96% for fluorescence in-situ hybridisation and 3.85% for dual in-situ hybridisation. Cases that failed for fluorescence in-situ hybridisation were successful for dual in-situ hybridisation and vice versa. Our study showed that dual in-situ hybridisation is a reliable and useful option for HER2 testing in breast cancer.

To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. Retrospective study. Department of Clinical Oncology in a public hospital in Hong Kong. All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.

Objectives: To compare the PathVysion fluorescence in-situ hybridisation assay with the INFORM HER2 Dual in-situ hybridisation assay on 104 invasive breast cancers with a broad spectrum of immunohistochemistry scores. Methods: This case series involved consecutive patients diagnosed with invasive breast carcinoma with equivocal immunohistochemistry score and referred for further HER2 assessment from the departments of Surgery and/or Clinical Oncology of the two hospitals between January 2013 and February 2014. An additional 10 cases with negative HER2 immunohistochemistry and 11 cases with positive HER2 immunohistochemistry were further included. Results: The results of both fluorescence in-situ hybridisation and dual in-situ hybridisation were available in 99 of 104 cases, respectively. Student’st test showed no statistically significant difference in the mean number of HER2 count, CEP17 copies, or HER2/CEP17 ratio between that obtained by fluorescence in-situ hybridisation and that obtained by dual in-situ hybridisation. Pearson’s correlation of results for the two assays was strong for HER2/CEP17 signal ratio (R=0.963, P<0.001) and mean HER2 copies per nucleus (R=0.897, P<0.001). Overall agreement was 96.0% (95 out of 99 cases, ĸ=0.882). Three of the four discordant cases were equivocal for either fluorescence in-situ hybridisation or dual in-situ hybridisation. The results of immunohistochemistry 0/1+ and 3+ cases showed 100% concordance between the two assays. The failure rate was 0.96% for fluorescence in-situ hybridisation and 3.85% for dual in-situ hybridisation. Cases that failed for fluorescence in-situ hybridisation were successful for dual in-situ hybridisation and vice versa. Conclusions: Our study showed that dual in-situ hybridisation is a reliable and useful option for HER2 testing in breast cancer.

Exact analytic expressions for planetary orbits and light trajectories in the Schwarzschild geometry are presented. A new parameter space is used to characterize all possible planetary orbits. Different regions in this parameter space can be associated with different characteristics of the orbits. The boundaries for these regions are clearly defined. Observational data can be directly associated with points in the regions. A possible extension of these considerations with an additional parameter for the case of Kerr geometry is briefly discussed.

Exact analytic expressions for planetary orbits and light trajectories in the Reissner-Nordstrom geometry are presented. They are characterized in a map specified by three dimensionless parameters for the planetary orbits, while two dimensionless parameters are required to map the trajectories of light. Notable differences with the corresponding orbits and trajectories in the Schwarzschild geometry are indicated. In particular, when the energy and angular momentum of the planet are fixed, the precession angle of the orbit decreases as the net electric charge of the massive star or black hole increases. A similar result also holds for the deflection angle of a light ray.

It is shown that the lowest order general relativistic correction produces elliptic orbits with a non-Newtonian eccentricity.

All possible orbital trajectories and their analytical expressions in the Schwarzschild metric are presented in a single complete map characterized by two dimensionless parameters. While three possible pairs of parameters with different advantages are described, the parameter space that gives the most convenient reduction to the Newtonian case is singled out and used which leads to a new insight on Newtonian limits among other results. Numerous analytic relations are presented. A comparison is made with the widely used formulation and presentation given by S. Chandrasekhar.

Some features of a parametrized space of orbits in the Schwarzschild geometry are described.