HER2 expression in a molecularly defined cohort of endometrial cancer patients: The SPECTRUM study.

Background: HER2 antibody-drug conjugates like Trastuzumab deruxtecan (TDxd) have shown efficacy in HER2-low cancers, however the prevalence and clinical impact of HER2-low in endometrial cancer (EC) remains unclear. This study investigates HER2 expression in EC, focusing on HER2-low frequency, its distribution across histologic and molecular subtypes, intratumoral heterogeneity, and prognostic significance.

Methods: This retrospective analysis included EC patients categorized histologically and molecularly, using ASCO/CAP HER2 scoring guidelines for endometrial, gastric, and breast cancers.

Impact of a Mock OSCE on Student Confidence in Applying the Pharmacists' Patient Care Process.

The Medical and Pharmacy Student Collaboration (MAPSC) student organization at the University of Southern California, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, created an extracurricular, peer-led, virtual group mock objective structured clinical examination (MOSCE) to expose first-year pharmacy students (P1s) to the Pharmacists' Patient Care Process (PPCP). The purpose of this study is to evaluate the impact of a MAPSC MOSCE on P1s self-reported confidence in applying the PPCP and on patient communication, medication knowledge, and clinical skills.

The Prognostic Significance of Tumor-Infiltrating Lymphocytes, PD-L1, BRCA Mutation Status and Tumor Mutational Burden in Early-Stage High-Grade Serous Ovarian Carcinoma-A Study by the Spanish Group for Ovarian Cancer Research (GEICO).

Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO).

Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples.

The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days).

The Clonal Relationship Between the Ductal and Lobular Components of Mixed Ductal-Lobular Carcinomas Suggested a Ductal Origin in Most Tumors.

The relationship between the ductal and lobular components of invasive ductolobular carcinomas (IDLC) has not been fully elucidated. In this study, the molecular alterations of both components were analyzed in a series of 20 IDLC that were selected, not only by morphologic criteria, but also by the loss of E-cadherin expression in the lobular component. We found that 80% of tumors shared alterations of driver genes in both components, being PIK3CA the most common alteration.

Molecular Heterogeneity of High Grade Colorectal Adenocarcinoma.

High grade colorectal carcinomas (HG-CRCs), which comprise 15% of colorectal carcinomas, are underrepresented in reported molecular studies. Clinicopathological, immunohistochemical, and molecular features of 40 HG-CRCs are described. Moreover, glandular and solid areas of 25 tumors were separately analyzed.

Molecular Heterogeneity of Endometrioid Ovarian Carcinoma: An Analysis of 166 Cases Using the Endometrial Cancer Subrogate Molecular Classification.

Endometrioid ovarian carcinoma (EOC) has clinical and biological differences compared with other histologic types of ovarian carcinomas, but it shares morphologic and molecular features with endometrioid endometrial carcinoma. To analyze the molecular heterogeneity of EOC according to the new molecular classification of endometrial cancer and to evaluate the prognostic significance of this molecular classification, we have analyzed 166 early-stage EOC by immunohistochemistry for mismatch repair proteins and p53 expression, and by Sanger sequencing for the exonuclease domain of polymerase epsilon (POLE EDM). In addition, we have carried out next-generation sequencing analysis of tumors with POLE EDM mutations to confirm the ultramutated profile.

Mismatch Repair Deficiency in Ovarian Carcinoma: Frequency, Causes, and Consequences.

Mismatch repair deficiency (MMRD) is involved in the initiation of both hereditary and sporadic tumors. MMRD has been extensively studied in colorectal cancer and endometrial cancer, but not so in other tumors, such as ovarian carcinoma. We have determined the expression of mismatch repair proteins in a large cohort of 502 early-stage epithelial ovarian carcinoma entailing all the 5 main subtypes: high-grade serous carcinoma, endometrioid ovarian carcinoma (EOC), clear cell carcinoma (CCC), mucinous carcinoma, and low-grade serous carcinoma.

The PALBONET Trial: A Phase II Study of Palbociclib in Metastatic Grade 1 and 2 Pancreatic Neuroendocrine Tumors (GETNE-1407).

Lessons Learned: Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib.

Background: Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines.

The Frequency and Prognostic Significance of the Histologic Type in Early-stage Ovarian Carcinoma: A Reclassification Study by the Spanish Group for Ovarian Cancer Research (GEICO).

The frequency and prognostic significance of the histologic type in early-stage ovarian cancer (OC) is not as well established as in advanced stages. In addition, histologic typing based only on morphologic features may be difficult, especially in high-grade tumors. In this study, we have analyzed a prospective cohort of 502 early-stage OCs to investigate their frequency, immunohistochemical characteristics, and survival of the 5 main histologic types.

Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma.

Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone.

High Frequency of Activating Mutations in Invasive Lobular Breast Carcinoma with Pleomorphic Features.

Characterisation of molecular alterations of pleomorphic lobular carcinoma (PLC), an aggressive subtype of invasive lobular carcinoma (ILC), have not been yet completely accomplished. To investigate the molecular alterations of invasive lobular carcinoma with pleomorphic features, a total of 39 tumour samples (in situ and invasive lesions and lymph node metastases) from 27 patients with nuclear grade 3 invasive lobular carcinomas were subjected to morphological, immunohistochemical and massive parallel sequencing analyses. Our observations indicated that invasive lobular carcinomas with pleomorphic features were morphologically and molecularly heterogeneous.

Metabolomics-Driven Elucidation of Cellular Nitrate Tolerance Reveals Ascorbic Acid Prevents Nitroglycerin-Induced Inactivation of Xanthine Oxidase.

Glyceryl trinitrate (GTN) has found widespread use for the treatment of angina pectoris, a pathological condition manifested by chest pain resulting from insufficient blood supply to the heart. Metabolic conversion of GTN, a nitric oxide (NO) pro-drug, into NO induces vasodilation and improves blood flow. Patients develop tolerance to GTN after several weeks of continuous use, limiting the potential for long-term therapy.

High frequency of co-infection by Epstein-Barr virus types 1 and 2 in patients with multiple sclerosis.

Background: The existence of Epstein-Barr virus (EBV) strains specifically associated with multiple sclerosis (MS) is a matter of controversy. Little is also known about the prevalence of EBV types 1 and 2 in MS patients and the presence of co-infections by both strains.

Objective: To make EBV strain type assignment and compare the frequencies of types 1, 2 and co-infections by both in MS patients and healthy controls.

Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance.

Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome.

Methods And Results: Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs [10, 27, 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stress-response inhibitors.

Persistent monoclonality after histological remission in gastric mucosa-associated lymphoid tissue lymphoma treated with chemotherapy and/or surgery: influence of t(11;18)(q21;q21).

The purpose of this work was to study retrospectively the molecular response and outcome of 19 gastric mucosa associated lymphoid tissue (MALT) lymphoma patients achieving histological remission after chemotherapy or surgery. Immunoglobulin heavy chain variable (IgV(H)) gene rearrangements were studied by PCR in biopsies obtained at diagnosis and follow-up. Presence of t(11;18)(q21;q21) was studied by FISH or RT-PCR.

Analysis of Epstein-Barr virus strains and variants in classical Hodgkin's lymphoma by laser microdissection.

Epstein-Barr virus (EBV) seems to have an etiological role in the pathogenesis of classical Hodgkin's lymphoma (cHL). Studies of whole tissue DNA by polymerase-chain reaction (PCR) have shown a considerable number of cHL cases with co-infections by different EBV strains and variants, which apparently contradict the clonality of EBV in cHL previously demonstrated by Southern blot analysis. Due to the paucity of HRS cells in HL tissues, studies on single cell DNA are necessary to identify the specific cellular location (HRS cells and/or bystander B lymphocytes) of the EBV strains and variants present in tissue specimens.

Analysis of the Cycilin D1/p16/pRb Pathway in Parathyroid Adenomas.

Cyclin D1/p16/pRb pathway controlling G1-S cell cycle checkpoint is frequently altered in human tumors. Currently, scarce data are available for parathyroid tumors. We have studied 46 parathyroid adenomas (PTAs) and 12 normal parathyroid glands (PTGs) by immunohistochemistry with cyclin D1 (CD1), p16, pRb, and Ki-67 antibodies.

p53/MDM2 Pathway Aberrations in Parathyroid Tumors: p21(WAF-1) and MDM2 Are Frequently Overexpressed in Parathyroid Adenomas.

Parathyroid adenomas (PTAs) are the main cause of primary hyperparathyroidism. Cell cycle regulation in normal parathyroid tissue (NPT) and PTA remains largely unknown. We have systematically explored several components involved in the p53/MDM2/p19(ARF) pathway in PTA and compared the results were with NPT.

Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto-oncogene. This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFR alpha 1 as a coreceptor. In order to explore the role of RET, GFR alpha 1 and GDNF genes in the variation of phenotypes observed in MEN2A families, we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families (23 cases studied).

BsmI vitamin D receptor polymorphism and pathogenesis of parathyroid adenoma.

Introduction: The role of vitamin D receptor (VDR) gene polymorphism in the pathogenesis of hyperparathyrodism is not clear yet. The aim of this study was to examine the role of BsmI VDR gene polymorphism in patients with primary hyperparathyrodism (PHP) secondary to adenomas.

Material And Methods: Fifty-two postmenopausal women with PHP, mean age 64.

Oncogene expression in tumour cells of pediatric Hodgkin's disease in Argentina--correlation with Epstein Barr virus presence.

A new category of oncogenes regulating apoptosis, p53 and bcl-2, and the Epstein Barr virus (EBV) latent membrane protein-1 (LMP-1) have been related to Hodgkin's disease (HD) pathogenesis. We attempt to determine p53, mdm2, p21waf-1, bcl-2 and LMP-1 immunohistochemical expression in tissue sections from formalin-fixed, paraffin-embedded lymph node biopsies of pediatric HD. P53 was detected in the nucleus of Reed Sternberg cells and their variants (H-RS) in 68% of the HD cases.

HIV-associated oral pleomorphic B-cell malignant lymphoma.

A 48-year-old HIV-seropositive homosexual patient presented with an ulcerative lesion in the left side of the soft palate, extensively involving local soft tissue structures. On histologic evaluation the lesions appeared to be a large-cell high-grade B-cell pleomorphic lymphoma with anaplastic and plasmacytoid features harboring Epstein-Barr virus genome in the tumor cells. Although known to be associated with HIV infection, this is a rare subtype of a malignant lymphoma arising in a patient positive for HIV.

Absence of EBV genome in lymphoepithelioma-like carcinomas of the larynx.

Undifferentiated nasopharyngeal carcinomas are universally associated with Epstein-Barr virus (EBV). This association has been exclusively established in lymphoepithelioma-like carcinomas in some locations. The relationship between EBV and lymphoepithelioma-like carcinomas in the larynx is unknown.