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Histopathology Jan 2024Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational... (Review)
Review
Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Pathology, Molecular; Lung Neoplasms; Carcinoma; Mutation; B7-H1 Antigen
PubMed: 37936491
DOI: 10.1111/his.15080 -
Surgical Pathology Clinics Sep 2021Lymphoid malignancies are a broad and heterogeneous group of neoplasms. In the past decade, the genetic landscape of these tumors has been explored and cataloged in fine... (Review)
Review
Lymphoid malignancies are a broad and heterogeneous group of neoplasms. In the past decade, the genetic landscape of these tumors has been explored and cataloged in fine detail offering a glimpse into the mechanisms of lymphomagenesis and new opportunities to translate these findings into patient management. A myriad of studies have demonstrated both distinctive and overlapping molecular and chromosomal abnormalities that have influenced the diagnosis and classification of lymphoma, disease prognosis, and treatment selection.
Topics: Chromosome Aberrations; Humans; Lymphoma; Pathology, Molecular
PubMed: 34373101
DOI: 10.1016/j.path.2021.06.001 -
Seminars in Diagnostic Pathology Sep 2019Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis,... (Review)
Review
Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis, tumorigenesis, and immune function contribute to the development of these assays. However, each technique, if applied incorrectly or in ignorance, can lead to difficulties in execution or errors in interpretation. In this review of commonly used molecular diagnostic tests, including immunohistochemistry, microsatellite instability testing, chromosomal microarray testing, and conventional and next-generation sequencing, the emphasis will be on potential pitfalls and considerations for each platform. Emerging technologies that may be used in clinical applications in the near future will also be discussed. An understanding of the methodologies, advantages, and drawbacks of molecular assays will help pathologists aid in diagnostic and therapeutic decisions.
Topics: Humans; Molecular Diagnostic Techniques; Pathology, Molecular
PubMed: 31182318
DOI: 10.1053/j.semdp.2019.06.002 -
Clinics in Laboratory Medicine Jun 2024
Topics: Humans; Pathology, Molecular; Molecular Diagnostic Techniques
PubMed: 38821650
DOI: 10.1016/j.cll.2024.03.001 -
Endocrine Pathology Mar 2021
Topics: Endocrine Gland Neoplasms; Endocrinology; Humans; Pathology, Molecular; Practice Patterns, Physicians'; Publishing
PubMed: 33624136
DOI: 10.1007/s12022-021-09670-5 -
Pathologie (Heidelberg, Germany) Aug 2022Odontogenic tumors (OTs) are rare, with an estimated incidence rate of less than 0.5 cases per 100,000 per year. The causes of OTs remain unclear. Nonetheless, the... (Review)
Review
BACKGROUND
Odontogenic tumors (OTs) are rare, with an estimated incidence rate of less than 0.5 cases per 100,000 per year. The causes of OTs remain unclear. Nonetheless, the majority of OTs seem to arise de novo, without an apparent causative factor. Although the etiopathogenesis of most OTs remains unclear, there have been some recent advances in understanding the genetic basis relating to specific histologies and clinical features. Molecular analyses performed by different techniques, including Sanger sequencing, next-generation sequencing, and allele-specific PCR, have uncovered mutations in genes related to the oncogenic MAPK/ERK signaling pathway. Genetic mutations in these pathway genes have been reported in epithelial and mixed OTs, in addition to odontogenic carcinomas and sarcomas. Notably, B‑RAF proto-oncogene serine/threonine kinase (BRAF) and KRAS proto-oncogene GTPase (KRAS) pathogenic mutations have been reported in a high proportion of ameloblastoma and ameloblastoma-related tumors and adenomatoid odontogenic tumors, respectively.
OBJECTIVE
To discuss how molecular profiling aids in diagnostic classification of odontogenic tumors.
CONCLUSION
Molecular profiling of odontogenic tumors helps to identify patients for neoadjuvant therapies and reduces postoperative morbidity.
Topics: Humans; Ameloblastoma; Odontogenic Tumors; Pathology, Molecular; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 36378285
DOI: 10.1007/s00292-022-01152-7 -
Annual Review of Genomics and Human... Aug 2022Molecular diagnostic tests enable rapid analysis of genomic and proteomic markers. These tests are subject to diverging premarket access and postmarket surveillance... (Review)
Review
Molecular diagnostic tests enable rapid analysis of genomic and proteomic markers. These tests are subject to diverging premarket access and postmarket surveillance requirements and mechanisms in the United States and the European Union. Each of these jurisdictions has its own challenges in keeping the regulations up to date with technological developments. A specific area of attention is that of laboratory-developed tests in the United States and health institution in-house-produced tests in the European Union, for which the United States and the European Union have markedly different regulatory approaches. Both jurisdictions have specific but differing requirements for the use of test samples and test-related data under their rules regarding the protection of (personal) health data, which can cause complexity when moving samples or sample-related data from one jurisdiction to the other.
Topics: European Union; Humans; Pathology, Molecular; Proteomics; United States; United States Food and Drug Administration
PubMed: 36044907
DOI: 10.1146/annurev-genom-121521-010416 -
EBioMedicine Nov 2021To reduce the high incidence and mortality of gastric cancer (GC), we aimed to develop deep learning-based models to assist in predicting the diagnosis and overall...
BACKGROUND
To reduce the high incidence and mortality of gastric cancer (GC), we aimed to develop deep learning-based models to assist in predicting the diagnosis and overall survival (OS) of GC patients using pathological images.
METHODS
2333 hematoxylin and eosin-stained pathological pictures of 1037 GC patients were collected from two cohorts to develop our algorithms, Renmin Hospital of Wuhan University (RHWU) and the Cancer Genome Atlas (TCGA). Additionally, we gained 175 digital pictures of 91 GC patients from National Human Genetic Resources Sharing Service Platform (NHGRP), served as the independent external validation set. Two models were developed using artificial intelligence (AI), one named GastroMIL for diagnosing GC, and the other named MIL-GC for predicting outcome of GC.
FINDINGS
The discriminatory power of GastroMIL achieved accuracy 0.920 in the external validation set, superior to that of the junior pathologist and comparable to that of expert pathologists. In the prognostic model, C-indices for survival prediction of internal and external validation sets were 0.671 and 0.657, respectively. Moreover, the risk score output by MIL-GC in the external validation set was proved to be a strong predictor of OS both in the univariate (HR = 2.414, P < 0.0001) and multivariable (HR = 1.803, P = 0.043) analyses. The predicting process is available at an online website (https://baigao.github.io/Pathologic-Prognostic-Analysis/).
INTERPRETATION
Our study developed AI models and contributed to predicting precise diagnosis and prognosis of GC patients, which will offer assistance to choose appropriate treatment to improve the survival status of GC patients.
FUNDING
Not applicable.
Topics: Algorithms; Area Under Curve; Biomarkers, Tumor; Deep Learning; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Neoplasm Grading; Neoplasm Staging; Pathology, Molecular; ROC Curve; Retrospective Studies; Stomach Neoplasms
PubMed: 34678610
DOI: 10.1016/j.ebiom.2021.103631 -
Genes, Chromosomes & Cancer Jun 2022Sarcomas are cancers of mesenchymal origin with the potential to arise in diverse anatomic locations. With over 80 subtypes, which often demonstrate overlapping... (Review)
Review
Sarcomas are cancers of mesenchymal origin with the potential to arise in diverse anatomic locations. With over 80 subtypes, which often demonstrate overlapping morphologies, sarcomas frequently require ancillary testing to enable accurate classification. Pathognomonic driver mutations can often be leveraged for diagnostic purposes and include fusion genes, amplification events, and recurrent point mutations. Until relatively recently, the major clinical molecular diagnostic tests have been karyotyping, fluorescence in situ hybridization, and polymerase chain reaction; however, these techniques have a number of limitations. Recent technological advances have led to the development of more comprehensive assays with higher throughput, thereby replacing the need for a suite of single gene tests. These approaches include next-generation sequencing, fluorescent bar code hybridization, and DNA methylation profiling, among others. Herein, we review the application of recently developed techniques relevant to the diagnosis of sarcomas, and emerging assays with the potential for future development and clinical implementation.
Topics: High-Throughput Nucleotide Sequencing; Humans; In Situ Hybridization, Fluorescence; Pathology, Molecular; Sarcoma; Soft Tissue Neoplasms
PubMed: 35064596
DOI: 10.1002/gcc.23025 -
American Journal of Transplantation :... Apr 2022
Topics: Allografts; Bronchiolitis Obliterans; Graft Rejection; Humans; Lung; Lung Transplantation; Pathology, Molecular
PubMed: 34910363
DOI: 10.1111/ajt.16925