Analytical Validation and Performance Evaluation of Amplicon-Based Next-Generation Sequencing Assays for Detecting and Other Gene Amplifications in Solid Tumors.

Background: Targeted next-generation sequencing (NGS) panels are increasingly being utilized to identify actionable gene amplifications (copy number > 4) among solid tumors.

Methods: This study validated the analytical performance of two amplicon-based NGS assays, the Oncomine Comprehensive Panel (OCAv3) and the Oncomine Focus Assay (OFA), for detecting gene amplification in formalin-fixed paraffin-embedded (FFPE) tumors of varying cellularity. OCAv3 was assessed for amplification detection in 756 FFPE samples comprising various tumor types.

Advances in Vulvar Cancer Biology and Management.

Purpose: Vulvar squamous cell carcinoma (VSCC), a rare gynecologic malignancy, has been rising in incidence. Molecular classification on the basis of human papilloma virus (HPV) and tumor protein 53 (p53) status has identified three clinically distinct subtypes, but we still treat all VSCCs the same. Here, we review molecular classification of VSCC, outline treatment landscape, and highlight potential for targeted therapies in advanced VSCC.

Implementation of HER2 Testing in Endometrial Cancer, a Summary of Real-World Initial Experience in a Large Tertiary Cancer Center.

HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we report on the initial two-year experience of HER2 testing at a major academic center with a reference gynecologic oncology service and biomarker reference laboratory.

Fit-for-Purpose Ki-67 Immunohistochemistry Assays for Breast Cancer.

New therapies are being developed for breast cancer, and in this process, some "old" biomarkers are reutilized and given a new purpose. It is not always recognized that by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer.

Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

Purpose: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM).

Methods: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied.

Methylation Testing as an Integral Component of Universal Endometrial Cancer Screening-A Critical Appraisal.

MLH1/PMS2 loss due to promoter hypermethylation (-PHM) is the most common cause of mismatch repair (MMR) deficiency in endometrial cancer (EC). This study aimed to determine the proportion of -deficient EC with PHM, assess the impact of the reflex -PHM testing strategy, and evaluate the associated costs within the publicly funded Canadian healthcare system. In a cohort of 2504 EC samples, 534 (21.

Budget impact analysis of molecular subtype profiling in endometrial cancer.

Objective: This study evaluated the costs associated with four approaches to classifying endometrial cancer (EC), including histomorphological, histomorphological with ancillary immunohistochemical assays, histomolecular and selective molecular classification.

Methods: Direct costs were determined per EC sample from the hospital's perspective. A budget impact analysis and sensitivity analysis were conducted to estimate the mean, minimum and maximum costs per sample and annual institutional costs in adjusted 2022 Canadian dollars.

Ki67 in Breast Cancer Assay: An Ad Hoc Testing Recommendation from the Canadian Association of Pathologists Task Force.

Ki67, a marker of cellular proliferation, is commonly assessed in surgical pathology laboratories. In breast cancer, Ki67 is an established prognostic factor with higher levels associated with worse long-term survival. However, Ki67 IHC is considered of limited clinical use in breast cancer management largely due to issues related to standardization and reproducibility of scoring across laboratories.

The Impact of the Pathologist in Multidisciplinary Cancer Conferences on Patient Care : Evidence From the Literature.

Objectives: Multidisciplinary cancer conferences (MCCs) are important tools in the treatment of patients with complex health issues, helping clinicians achieve optimal outcomes in oncological practice. To explore the role of pathologists at MCCs, we conducted a review of prior research on this topic.

Methods: We conducted a scoping review by searching MEDLINE, EMBASE, and the Cochrane Library for English-language qualitative, quantitative, or multiple/mixed methods studies on the role and impact of pathologists on MCCs.

Cystic neutrophilic granulomatous mastitis: sensitivity and specificity of 16s rRNA and Sanger sequencing for spp.

Aims: Cystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with spp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases.

Methods: Breast specimens diagnosed as granulomatous inflammation between 2010 and 2020 were reviewed to identify a CNGM cohort and a non-CNGM cohort.

Gynecologic pathology services in low- and middle-income countries.

Objective: The International Gynecologic Cancer Society (IGCS) offers multidisciplinary conferences to underserved communities. Mentor pathologists have become an integral part of these tumor boards, as pathology services in low-to-middle-income countries are often inadequate and disjointed. The IGCS Pathology Working Group conducted a survey to assess barriers to quality pathology services in low-to-middle-income countries and identified potential solutions.

Interlaboratory Concordance of ProMisE Molecular Classification of Endometrial Carcinoma Based on Endometrial Biopsy Specimens.

Molecular classifiers improve the consistency of categorization of endometrial carcinoma and provide valuable prognostic information. We aimed to evaluate the interlaboratory agreement in ProMisE assignment across 3 dedicated Canadian gynecologic oncology centers. Fifty cases of endometrial carcinoma diagnosed on biopsy were collected from 3 centers and 3 unstained sections were provided to each participating site so that immunohistochemistry for MSH6, PMS2, and p53 could be performed and interpreted at each center, blinded to the original diagnoses and the results from other centers.

Performance Characteristics of Endometrial Sampling in Diagnosis of Endometrial Carcinoma.

Outpatient endometrial biopsy can give false-negative results, with a 0.9% reported posttest probability for endometrial carcinoma (EC) after a negative result. Our objective was to determine if there has been any improvement in the performance characteristics of endometrial biopsy over the last 15 yr.

Canadian Consensus-based and Evidence-based Guidelines for Benign Endometrial Pathology Reporting in Biopsy Material.

Standardized terminology has proven benefits in cancer reporting; in contrast, reporting of benign diagnoses in endometrial biopsy currently lacks such standardization. Unification and update on the lexicon can provide the structure and consistency needed for optimal patient care and quality assurance purposes. The Special Interest Group in Gynecologic Pathology of the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) embarked in an initiative to address the current need for consensus terminology in benign endometrial biopsy pathology reporting.

Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype.

Molecular profiling and clinical outcome of high-grade serous ovarian cancer presenting with low- versus high-volume ascites.

Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade.

Assessment of the prognostic significance of endoglin (CD105) in clear cell renal cell carcinoma using automated image analysis.

The behavior of clear cell renal cell carcinoma can be difficult to predict. Angiogenesis has proven to be a useful prognostic indicator in different malignancies. Endoglin (CD105) is a new marker of angiogenesis found to have prognostic utility in various tumors.

Disseminated intravascular coagulopathy in the first 24 hours after trauma: the association between ISTH score and anatomopathologic evidence.

Background: Recent studies questioned "classical" concepts in trauma care, including whether disseminated intravascular coagulation (DIC) occurs in trauma. The knowledge on trauma DIC is limited to few studies built on diagnosing DIC with laboratory-based scores. This study explores whether DIC diagnosed by the well-established ISTH (International Society for Thrombosis and Hemostasis) score is corroborated by anatomopathologic findings.

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study.

Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results.

Endometrial giant cell carcinoma: a case series and review of the spectrum of endometrial neoplasms containing giant cells.

Poorly differentiated endometrial carcinomas of specific type include the rarely reported endometrial carcinoma with a malignant giant cell component [endometrial giant cell carcinoma (GCC)]. Since the initial description in 1991, there has only been 1 subsequent case report of this entity. We report another 5 cases.

Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histologic features.

Purpose: To investigate relationships between magnetic resonance (MR) imaging measurements and the underlying composition of normal and malignant prostate tissue.

Materials And Methods: Twenty-four patients (median age, 63 years; age range, 44-72 years) gave informed consent to be examined for this research ethics board-approved study. Before undergoing prostatectomy, patients were examined with T2-weighted, diffusion-weighted, T2 mapping, and dynamic contrast material-enhanced MR imaging at 1.

Intraoperative consultation in gynecologic pathology: a 6-year audit at a tertiary care medical center.

Background: Most of the literature on intraoperative consultation (IOC) in gynecologic pathology focuses on the accuracy of this technique. This study addresses a wide range of quality assurance issues regarding this practice through a comprehensive audit of our experience.

Design: The anatomic pathology database was searched between 1999 and 2005 for all gynecologic cases who received IOCs.