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Virchows Archiv : An International... Feb 2024Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic... (Review)
Review
Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic adjuvant or neoadjuvant or in metastatic setting, but increasingly serve in diagnostic routine histopathological services to differentiate between morphologically overlapping or ambiguous histological pictures. Diagnostic tools involve in most cases a broad spectrum of immunohistochemical panels, followed by entity-specific in situ hybridization probes and in given cases NGS-based sequencing. Workflow of which methodology is applied and in which order depends on the specific entity resp. on the given differential diagnosis in question. Regarding prognostic/predictive molecular testing, the choice of assay and the workflow are based on clinical algorithms and on the evidence of targeted therapies following the molecular alterations. In this review paper, we aim to address the use of molecular technics in [1] the histological diagnostic setting (such as subtyping of invasive carcinomas/malignant spindle cell tumors and sarcomas and some B3 lesions) and [2] in the context of adjuvant or neoadjuvant or other clinical settings with special focus of targeted therapies.
Topics: Humans; Female; Prognosis; Pathology, Molecular; Breast Neoplasms; Sarcoma; Carcinoma
PubMed: 38015260
DOI: 10.1007/s00428-023-03709-0 -
Frontiers in Psychiatry 2023
PubMed: 37829758
DOI: 10.3389/fpsyt.2023.1286182 -
International Journal of Molecular... Jul 2023Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed... (Review)
Review
Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.
Topics: Humans; Male; Biopsy; Oncogene Proteins, Fusion; Prostate; Prostatic Neoplasms; Serine Endopeptidases; Transcriptional Regulator ERG; p300-CBP Transcription Factors
PubMed: 37511059
DOI: 10.3390/ijms241411299 -
Cancers Dec 2023Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and... (Review)
Review
Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz-Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli-Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.
PubMed: 38136408
DOI: 10.3390/cancers15245864 -
Biomedicines Dec 2023This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment... (Review)
Review
This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment approaches, including surgery, radiotherapy, chemotherapy, and their integration with newer treatments. Key to the discussion is the role of biomarkers in oncology for risk assessment, diagnosis, prognosis, and the monitoring of pituitary adenomas. We highlight advances in genomic, epigenomic, and transcriptomic analyses and their contributions to understanding the pathogenesis and molecular pathology of these tumors. Special attention is given to the molecular mechanisms, including the impact of epigenetic factors like histone modifications, DNA methylation, and transcriptomic changes on different subtypes of pituitary adenomas. The importance of the tumor immune microenvironment in tumor behavior and treatment response is thoroughly analyzed. We highlight potential breakthroughs and innovations for a more effective management and treatment of pituitary adenomas, while shedding light on the ongoing need for research and development in this field to translate scientific knowledge into clinical advancements, aiming to improve patient outcomes.
PubMed: 38275385
DOI: 10.3390/biomedicines12010023 -
Frontiers in Oral Health 2023
PubMed: 37601298
DOI: 10.3389/froh.2023.1256495 -
The Journal of Molecular Diagnostics :... Dec 2023Diagnosing, selecting therapy for, and monitoring cancer in patients using a minimally invasive blood test represents a significant advance in precision medicine. Wide... (Review)
Review
Diagnosing, selecting therapy for, and monitoring cancer in patients using a minimally invasive blood test represents a significant advance in precision medicine. Wide variability exists in how circulating tumor DNA (ctDNA) assays are developed, validated, and reported in the literature, which hinders clinical adoption and may negatively impact patient care. Standardization is needed for factors affecting ctDNA assay performance and reporting, including pre-analytical variables, analytical considerations, and elements of laboratory assay reporting. The Association for Molecular Pathology Clinical Practice Committee's Liquid Biopsy Working Group (LBxWG), including organizational representation from the American Society of Clinical Oncology and the College of American Pathologists, has undertaken a full-text data extraction of 1228 ctDNA publications that describe assays performed in patients with lymphoma and solid tumor malignancies. With an emphasis on clinical assay validation, the LBxWG has developed a set of 13 best practice consensus recommendations for validating, reporting, and publishing clinical ctDNA assays. Recommendations include reporting key pre-analytical considerations and assay performance metrics; this analysis demonstrates these elements are inconsistently included in publications. The LBxWG recommendations are intended to assist clinical laboratories with validating and reporting ctDNA assays and to ensure high-quality data are included in publications. It is expected that these recommendations will need to be updated as the body of literature continues to mature.
Topics: Humans; United States; Cell-Free Nucleic Acids; Pathology, Molecular; Consensus; Pathologists; Neoplasms
PubMed: 37806433
DOI: 10.1016/j.jmoldx.2023.09.004 -
The Journal of Investigative Dermatology Sep 2023Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune...
Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies in melanoma. We assessed a unique cohort of eight melanoma samples with focal loss of PTEN protein expression to understand the features and mechanisms of PTEN loss in this disease. We compared the PTEN-negative (PTEN[-]) areas to their adjacent PTEN-positive (PTEN[+]) areas using DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemical platforms. Variations or homozygous deletions of PTEN were identified in PTEN(-) areas that were not detected in the adjacent PTEN(+) areas in three cases (37.5%), but no clear genomic or DNA methylation basis for loss was identified in the remaining PTEN(-) samples. RNA expression data from two independent platforms identified a consistent increase in chromosome segregation gene expression in PTEN(-) versus adjacent PTEN(+) areas. Proteomic analysis showed a relative paucity of tumor-infiltrating lymphocytes in PTEN(-) versus adjacent PTEN(+) areas. The findings add to our understanding of potential molecular intratumoral heterogeneity in melanoma and the features associated with the loss of PTEN protein in this disease.
Topics: Humans; PTEN Phosphohydrolase; Proteomics; Melanoma; Genes, Tumor Suppressor; RNA
PubMed: 36871660
DOI: 10.1016/j.jid.2023.01.034 -
Biomedicine & Pharmacotherapy =... May 2024Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates... (Review)
Review
Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates the patient's quality of life, and it imposes significant social and economic burdens. The molecular pathology of IVDD is highly complex and multilateral however still not ompletely understood. New findings indicate that IVDD is closely associated with inflammation, oxidative stress, cell injury and extracellular matrix metabolismdysregulation. Symptomatic management is the main therapeutic approach adopted for IVDD, but it fails to address the basic pathological changes and the causes of the disease. However, research is still focusing on molecular aspects in terms of gene expression, growth factors and cell signaling pathways in an attempt to identify specific molecular targets for IVDD treatment. The paper summarizes the most recent achievements in molecularunderstanding of the pathogenesis of IVDD and gives evidence-based recommendations for clinical practice.
Topics: Intervertebral Disc Degeneration; Humans; Animals; Oxidative Stress; Signal Transduction; Intervertebral Disc; Extracellular Matrix
PubMed: 38626521
DOI: 10.1016/j.biopha.2024.116593 -
Pathologie (Heidelberg, Germany) Sep 2023Ovarian cancer is a common malignant genital neoplasm in women. Due to its frequent diagnosis only in advanced stages, prognosis is poor, although biomarker-driven...
Ovarian cancer is a common malignant genital neoplasm in women. Due to its frequent diagnosis only in advanced stages, prognosis is poor, although biomarker-driven targeted therapeutic approaches are evolving. These are currently based on molecular pathological analyses of homologous recombination deficiency (HRD) and the BRCA1/2 mutational status. The current CME article focuses on the histo- and molecular pathology of ovarian cancer, relevant molecular mechanisms, and test systems. These are discussed in the context of biomarker-driven targeted therapy.
Topics: Female; Humans; BRCA1 Protein; Pathology, Molecular; Molecular Targeted Therapy; BRCA2 Protein; Ovarian Neoplasms
PubMed: 37584749
DOI: 10.1007/s00292-023-01214-4