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J. Mol. Pathol., Volume 4, Issue 1 (March 2023) – 7 articles

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12 pages, 10946 KiB  
Article
Fluorescence In Situ Hybridization (FISH) for the Characterization and Monitoring of Primary Cultures from Human Tumors
by Ruth Román-Lladó, Cristina Aguado, Núria Jordana-Ariza, Jaume Roca-Arias, Sonia Rodríguez, Erika Aldeguer, Mónica Garzón-Ibañez, Beatriz García-Peláez, Marta Vives-Usano, Ana Giménez-Capitán, Andrés Aguilar, Alejandro Martinez-Bueno, María Gonzalez Cao, Florencia García-Casabal, Santiago Viteri, Clara Mayo de las Casas, Rafael Rosell and Miguel Angel Molina-Vila
J. Mol. Pathol. 2023, 4(1), 57-68; https://doi.org/10.3390/jmp4010007 - 14 Mar 2023
Viewed by 2370
Abstract
Genetic and drug sensitivity assays on primary cultures are not only of basic but also of translational interest and could eventually aid oncologists in the selection of treatments. However, cancer cells need to be identified and differentiated from the non-tumor cells always present [...] Read more.
Genetic and drug sensitivity assays on primary cultures are not only of basic but also of translational interest and could eventually aid oncologists in the selection of treatments. However, cancer cells need to be identified and differentiated from the non-tumor cells always present in primary cultures. Also, successive passages can change the proportions of these two subpopulations. In this study, we propose fluorescence in situ hybridization (FISH) analysis on cell smears to determine the presence of tumor cells in primary cultures obtained from patients carrying translocations or copy number gains. FISH proved to be an easy, fast, economic, and reliable method of characterizing cell populations, which could be used repeatedly at different passages to monitor variations and to confirm the maintenance of translocations and copy number gains throughout the culture process. Full article
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11 pages, 1170 KiB  
Article
MET Exon 14 Variants in Non-Small Cell Lung Carcinoma: Prevalence, Clinicopathologic and Molecular Features
by Lisi Yuan, Harshita Mehrotra, Xin He and David Bosler
J. Mol. Pathol. 2023, 4(1), 46-56; https://doi.org/10.3390/jmp4010006 - 09 Feb 2023
Viewed by 2222
Abstract
Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review [...] Read more.
Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review of all MET ex14 tested NSCLC. Testing for selected BRAF, EGFR, HER2, KRAS, and MET mutations was performed using a clinically validated NGS assay, followed by MiSeq sequencing. Variants were classified as significant (Tier1/2) or variants of uncertain significance (VUS) per 2017 AMP/ASCO/CAP Joint Consensus Guidelines. PD-L1 expression was assessed by immunohistochemistry. Results: Of 2296 NSCLCs tested between 2017-7/2019, MET ex14 variants were present in 44 (1.9%). A total of 32 of 44 variants were MET exon 14 skipping, while the other 12 mutations were significant missense (3) or VUS (9). Of nine VUS, five were adjacent to the canonical splice site and likely to impact splicing. Four cases had concomitant mutations. Of 35 cases with known clinical staging, stage 1–2 = 20 (57%), stage 3 = 3 (9%), and stage 4 = 12 (34%). Of 19 resected NSCLSs, histological types and growth pattern included 7 lepidic pattern-predominant. A high percentage of tumors with MET ex14 mutations are positive for PD-L1, and the percentage of cases with PD-L1 expression >50% trends higher in more advanced disease. Conclusions: Most MET variants identified in our cohort (73%) are MET ex14 skipping. The prevalence of MET ex14 variants is 1.9%, and a large percentage of tumors has lower clinical stage and less aggressive pathologic features. Full article
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2 pages, 249 KiB  
Editorial
Acknowledgment to the Reviewers of Journal of Molecular Pathology in 2022
by JMP Editorial Office
J. Mol. Pathol. 2023, 4(1), 44-45; https://doi.org/10.3390/jmp4010005 - 17 Jan 2023
Viewed by 1171
Abstract
High-quality academic publishing is built on rigorous peer review [...] Full article
13 pages, 918 KiB  
Article
Mutational Profiling of Lung Cancer Using Next Generation Sequencing: A Malaysian Real-World Clinical Diagnostic Experience
by Pathmanathan Rajadurai, Ning Yi Yap, Saira Bahnu Mohamed Yousoof and Yoke Kqueen Cheah
J. Mol. Pathol. 2023, 4(1), 31-43; https://doi.org/10.3390/jmp4010004 - 11 Jan 2023
Cited by 2 | Viewed by 4325
Abstract
Lung cancer is one of the most common cancers and a leading cause of cancer-related mortality in Malaysia. This analysis aimed to evaluate the prevalence of actionable and common mutations, as well as co-mutations frequently occurring with EGFR variants in lung cancer. Mutational [...] Read more.
Lung cancer is one of the most common cancers and a leading cause of cancer-related mortality in Malaysia. This analysis aimed to evaluate the prevalence of actionable and common mutations, as well as co-mutations frequently occurring with EGFR variants in lung cancer. Mutational profiling of lung tumour samples was performed using next generation sequencing (NGS) panels at the Subang Jaya Medical Centre laboratory. A total of 469 lung tumour samples referred from several medical facilities in Malaysia were analysed and 84% were of the adenocarcinoma subtype. The three most frequent mutations found were EGFR (46.5%), TP53 (37.5%) and KRAS (14.3%). Actionable mutations with approved drug targets for lung cancer were detected in 63.5% of patient samples. Among patients with EGFR mutations, deletions in exon 19 were detected in 44.5% and p.L858R in 38.5% of samples. The most common co-mutations for samples with EGFR mutations were found in the TP53 gene (38.1%). A median turnaround time (TAT) of 3 working days was achievable with an automated NGS platform. NGS testing can provide valuable information on the mutational landscape and the prevalence of common or actionable mutations present in lung cancer patients. This real-world experience demonstrates the high percentage of actionable mutations detected and highlights the value of NGS testing in a clinical diagnostic setting. Full article
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3 pages, 190 KiB  
Editorial
Juggling the Various Facets of Modern Anatomic Pathology: A Perspective
by Pasquale Pisapia and Giancarlo Troncone
J. Mol. Pathol. 2023, 4(1), 28-30; https://doi.org/10.3390/jmp4010003 - 09 Jan 2023
Viewed by 1060
Abstract
Anatomic pathology, along with the role of anatomic pathologists, has significantly evolved over the past several years [...] Full article
(This article belongs to the Collection Juggling the Various Facets of Modern Anatomic Pathology)
13 pages, 807 KiB  
Article
Platelet Concentration and Platelet/Lymphocyte Ratio as Prognostic Indicators in Luminal Breast Cancer
by Angela Della’Santa Rubio O. Rönnau, Maiquidieli Dal Berto, Claudia Giuliano Bica, Rafael Vargas Alves and Liane Nanci Rotta
J. Mol. Pathol. 2023, 4(1), 15-27; https://doi.org/10.3390/jmp4010002 - 02 Jan 2023
Cited by 1 | Viewed by 1990
Abstract
Ratios between the blood cells are indirect measures of the imbalance in the pro-inflammatory status observed in carcinogenesis and have been proposed as accessible and feasible biomarkers to predict cancer prognosis. We aim to evaluate the prognostic significance of neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), [...] Read more.
Ratios between the blood cells are indirect measures of the imbalance in the pro-inflammatory status observed in carcinogenesis and have been proposed as accessible and feasible biomarkers to predict cancer prognosis. We aim to evaluate the prognostic significance of neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios in Brazilian patients with luminal breast cancer (LBC) treated with tamoxifen. A retrospective cohort of 72 operable LBC patients. Preoperative leukocyte and platelet absolute values permitted to calculate NLR, MLR, and PLR. Area under curve (ROC) determined the cutoff value associated with relapse and death. Univariate and multivariate analyses were used to assess the relationship of the platelet and PLR to disease-free survival (DFS) and overall survival (OS). Lower DFS was associated with >297 × 103/mm3 (54 vs. 60.9 months in <297, p = 0.04). Platelet > 279 × 103/mm3 are related to higher OS (p = 0.03). Univariate analysis revealed that platelet concentration was associated with DFS (p = 0.04) and OS (p = 0.04), but not as an independent factor (HR = 1.31, 95%CI: 0.42–4.07, p = 0.65) and OS (HR = 1.64, 95%CI: 0.28–9.52, p = 0.58). Both univariate (p = 0.01) and multivariate analysis revealed that PLR < 191.5 was a significant independent predictor of higher OS/better prognosis (HR = 16.16, 95%CI: 2.83–109.25, p = 0.00). Pretreatment platelet indices (absolute count and PLR) are prognosis predictors in LBC patients. Platelet > 279 × 103/mm3 and PRL < 191.5 was associated with a higher OS, with the PRL being an independent predictor of higher OS. Full article
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14 pages, 4086 KiB  
Review
Metastatic Breast Cancer: Cytology Diagnosis with Implications for Treatment
by Alaa Hrizat and Elena Brachtel
J. Mol. Pathol. 2023, 4(1), 1-14; https://doi.org/10.3390/jmp4010001 - 24 Dec 2022
Cited by 3 | Viewed by 3859
Abstract
Breast cancer is among the most frequent malignancies in women worldwide. While early detection and effective treatment provide many women with a cure and prevent their cancer from spreading, metastases to distant sites still occur in around 20% of women suffering from breast [...] Read more.
Breast cancer is among the most frequent malignancies in women worldwide. While early detection and effective treatment provide many women with a cure and prevent their cancer from spreading, metastases to distant sites still occur in around 20% of women suffering from breast cancer. These relapses occur in many forms and locations and are as varied as the primary breast tumors. Metastatic spread makes a cancer incurable and potentially lethal, but new, targeted treatments can offer control of the cancer cells if the features of new targets are unlocked by advanced diagnostic testing. The article offers an overview of the pathomechanisms of metastatic progression and describes the types of metastases, such as hormone-receptor-positive and -negative breast cancers, and HER2-overexpressing or triple-negative types. Once distant metastatic spread occurs, cytology allows a precise diagnosis to confirm the breast origin. Other molecular targets include ESR1 and PIK3CA mutations, MSI, NTRK fusion, PD-L1 expression and others, which can be obtained also from cytology material and used to determine eligibility for emerging targeted therapeutic options. We outline the diagnostic features of metastatic breast cancer in cytology samples, together with validated and emergent biomarkers that may provide new, targeted treatment options. Full article
(This article belongs to the Special Issue The Cytopathology of Metastatic Breast Cancer)
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