Clinical and molecular assessment of an onco-immune signature with prognostic significance in patients with colorectal cancer.

Understanding the complex tumor microenvironment is key to the development of personalized therapies for the treatment of cancer including colorectal cancer (CRC). In the past decade, significant advances in the field of immunotherapy have changed the paradigm of cancer treatment. Despite significant improvements, tumor heterogeneity and lack of appropriate classification tools for CRC have prevented accurate risk stratification and identification of a wider patient population that may potentially benefit from targeted therapies. To identify novel signatures for accurate prognostication of CRC, we quantified gene expression of 12 immune-related genes using a medium-throughput NanoString quantification platform in 93 CRC patients. Multivariate prognostic analysis identified a combined four-gene prognostic signature (TGFB1, PTK2, RORC, and SOCS1) (HR: 1.76, 95% CI: 1.05-2.95, *p < 0.02). The survival trend was captured in an independent gene expression data set: GSE17536 (177 patients; HR: 3.31, 95% CI: 1.99-5.55, *p < 0.01) and GSE14333 (226 patients; HR: 2.47, 95% CI: 1.35-4.53, *p < 0.01). Further, gene set enrichment analysis of the TCGA data set associated higher prognostic scores with epithelial-mesenchymal transition (EMT) and inflammatory pathways. Comparatively, a lower prognostic score was correlated with oxidative phosphorylation and MYC and E2F targets. Analysis of immune parameters identified infiltration of T-reg cells, CD8+ T cells, M2 macrophages, and B cells in high-risk patient groups along with upregulation of immune exhaustion genes. This molecular study has identified a novel prognostic gene signature with clinical utility in CRC. Therefore, along with prognostic features, characterization of immune cell infiltrates and immunosuppression provides actionable information that should be considered while employing personalized medicine.

Clinical performance and utility of a comprehensive next-generation sequencing DNA panel for the simultaneous analysis of variants, TMB and MSI for myeloid neoplasms.

The extensively employed limited-gene coverage NGS panels lead to clinically inadequate molecular profiling of myeloid neoplasms. The aim of the present investigation was to assess performance and clinical utility of a comprehensive DNA panel for myeloid neoplasms. Sixty-one previously well characterized samples were sequenced using TSO500 library preparation kit on NextSeq550 platform. Variants with a VAF ≥ 5% and a total read depth of >50X were filtered for analysis. The following results were recorded-for clinical samples: clinical sensitivity (97%), specificity (100%), precision (100%) and accuracy (99%) whereas reference control results were 100% for analytical sensitivity, specificity, precision and accuracy, with high intra- and inter-run reproducibility. The panel identified 880 variants across 292 genes, of which, 749 variants were in genes not covered in the 54 gene panel. The investigation revealed 14 variants in ten genes, and at least one was present in 96.2% patient samples that were pathogenic/ likely pathogenic in myeloid neoplasms. Also, 15 variants in five genes were found to be pathogenic/ likely pathogenic in other tumor types. Further, the TMB and MSI scores ranged from 0-7 and 0-9, respectively. The high analytical performance and clinical utility of this comprehensive NGS panel makes it practical and clinically relevant for adoption in clinical laboratories for routine molecular profiling of myeloid neoplasms.

The Recent Pathology Residency Graduate Job Search Experience: A Synthesis of 5 Years of College of American Pathologists Job Market Surveys.

CONTEXT: - Pathology residents and fellows tailor their training and job search strategies to an actively evolving specialty in the setting of scientific and technical advances and simultaneous changes in health care economics. OBJECTIVE: - To assess the experience and outcome of the job search process of pathologists searching for their first non-fellowship position. DESIGN: - The College of American Pathologists (CAP) Graduate Medical Education Committee has during the past 5 years sent an annual job search survey each June to CAP junior members and fellows in practice 3 years or less who have actively searched for a non-fellowship position. RESULTS: - Job market indicators including job interviews, job offers, positions accepted, and job satisfaction have remained stable during the 5 years of the survey. Most survey respondents who had applied for at least 1 position had accepted a position at the time of the survey, and most applicants who had accepted a position were satisfied or very satisfied. However, most attested that finding a non-fellowship position was difficult. Despite a perceived push toward subspecialization in surgical pathology, the reported number of fellowships completed was stable. Respondent demographics were not associated with job search success with 1 significant exception: international medical school graduate respondents reported greater perceived difficulty in finding a position, and indeed, fewer reported having accepted a position. CONCLUSIONS: - Pathology residents and fellows seeking their first position have faced a relatively stable job market during the last 5 years, with most accepting positions with which they were satisfied.

Assessment and Management of Professionalism Issues in Pathology Residency Training: Results From Surveys and a Workshop by the Graduate Medical Education Committee of the College of American Pathologists.

Professionalism issues are common in residency training and can be very difficult to recognize and manage. Almost one-third of the milestones for pathology recently instituted by the Accreditation Council for Graduate Medical Education encompass aspects of professionalism. Program directors are often unsure of how and when to remediate residents for unprofessional behavior. We used a case-based educational approach in a workshop setting to assist program directors in the management of unprofessional behavior in residents. Eight case scenarios highlighting various aspects of unprofessional behavior by pathology residents were developed and presented in an open workshop forum at the annual pathology program director's meeting. Prior to the workshop, 2 surveys were conducted: (1) to collect data on program directors' experience with identifying, assessing, and managing unprofessional behavior in their residents and (2) to get feedback from workshop registrants on how they would manage each of the 8 case scenarios. A wide range of unprofessional behaviors have been observed by pathology program directors. Although there is occasionally general agreement on how to manage specific behaviors, there remains wide variation in how to manage many of the presented unprofessional behaviors. Remediation for unprofessional behavior in pathology residents remains a difficult and challenging process. Additional education and research in this area are warranted.