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Cancers
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Cancer Testing in the Modern Diagnostic Molecular Pathology Laboratory
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Cancer Testing in the Modern Diagnostic Molecular Pathology Laboratory

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (4 March 2021) | Viewed by 8100

Special Issue Editor

Dr. José Luís Costa

E-Mail Website
Guest Editor
i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
Ipatimup – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
Interests: molecular pathology; genomics; genetics

Special Issue Information

Dear Colleagues,

The advent of precision medicine in cancer treatment has changed the paradigm of cancer diagnosis. The increase in target therapies that rely on specific biomarker identification with the consequent move from single to multiple biomarker testing has led to the continuous development of new diagnostic strategies. This is strongly affecting the routine in diagnostic molecular pathology laboratories.

In this Special Issue, the modern diagnostic molecular pathology laboratory will be the focus. The Issue will cover how laboratories manage to provide accurate, reliable, and cost‐effective results, as well as the strategies for comprehensive molecular testing from their development to their implementation and clinical/analytical validation. Additionally, the Issue will cover the impact on how quality assurance and competence assessment of diagnostic molecular pathology laboratories are performed.

Dr. José Luís Costa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor testing
  • biomarkers
  • mutation
  • target therapy
  • diagnosis
  • technology
  • next-generation sequencing
  • precision medicine

Published Papers (3 papers)

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Research

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14 pages, 4093 KiB  
Article
Using the R Package Spatstat to Assess Inhibitory Effects of Microregional Hypoxia on the Infiltration of Cancers of the Head and Neck Region by Cytotoxic T Lymphocytes
by Justus Kaufmann, Christophe A. N. Biscio, Peter Bankhead, Stefanie Zimmer, Heinz Schmidberger, Ege Rubak and Arnulf Mayer
Cancers 2021, 13(8), 1924; https://doi.org/10.3390/cancers13081924 - 16 Apr 2021
Cited by 6 | Viewed by 2481
Abstract
(1) Background: The immune system has physiological antitumor activity, which is partially mediated by cytotoxic T lymphocytes (CTL). Tumor hypoxia, which is highly prevalent in cancers of the head and neck region, has been hypothesized to inhibit the infiltration of tumors by CTL. [...] Read more.
(1) Background: The immune system has physiological antitumor activity, which is partially mediated by cytotoxic T lymphocytes (CTL). Tumor hypoxia, which is highly prevalent in cancers of the head and neck region, has been hypothesized to inhibit the infiltration of tumors by CTL. In situ data validating this concept have so far been based solely upon the visual assessment of the distribution of CTL. Here, we have established a set of spatial statistical tools to address this problem mathematically and tested their performance. (2) Patients and Methods: We have analyzed regions of interest (ROI) of 22 specimens of cancers of the head and neck region after 4-plex immunofluorescence staining and whole-slide scanning. Single cell-based segmentation was carried out in QuPath. Specimens were analyzed with the endpoints clustering and interactions between CTL, normoxic, and hypoxic tumor areas, both visually and using spatial statistical tools implemented in the R package Spatstat. (3) Results: Visual assessment suggested clustering of CTL in all instances. The visual analysis also suggested an inhibitory effect between hypoxic tumor areas and CTL in a minority of the whole-slide scans (9 of 22, 41%). Conversely, the objective mathematical analysis in Spatstat demonstrated statistically significant inhibitory interactions between hypoxia and CTL accumulation in a substantially higher number of specimens (16 of 22, 73%). It showed a similar trend in all but one of the remaining samples. (4) Conclusion: Our findings provide non-obvious but statistically rigorous evidence of inhibition of CTL infiltration into hypoxic tumor subregions of cancers of the head and neck. Importantly, these shielded sites may be the origin of tumor recurrences. We provide the methodology for the transfer of our statistical approach to similar questions. We discuss why versions of the Kcross and pcf.cross functions may be the methods of choice among the repertoire of statistical tests in Spatstat for this type of analysis. Full article
(This article belongs to the Special Issue Cancer Testing in the Modern Diagnostic Molecular Pathology Laboratory)
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Review

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17 pages, 723 KiB  
Review
Liquid Biopsies in Solid Cancers: Implementation in a Nordic Healthcare System
by Oddmund Nordgård, Rakel Brendsdal Forthun, Morten Lapin, Bjørn Henning Grønberg, Karl Henning Kalland, Reidun Kristin Kopperud, Liv Cecilie Vestrheim Thomsen, Kjersti Tjensvoll, Bjørnar Gilje, Bjørn Tore Gjertsen and Randi Hovland
Cancers 2021, 13(8), 1861; https://doi.org/10.3390/cancers13081861 - 13 Apr 2021
Cited by 4 | Viewed by 2638
Abstract
Liquid biopsies have emerged as a potential new diagnostic tool, providing detailed information relevant for characterization and treatment of solid cancers. We here present an overview of current evidence supporting the clinical relevance of liquid biopsy assessments. We also discuss the implementation of [...] Read more.
Liquid biopsies have emerged as a potential new diagnostic tool, providing detailed information relevant for characterization and treatment of solid cancers. We here present an overview of current evidence supporting the clinical relevance of liquid biopsy assessments. We also discuss the implementation of liquid biopsies in clinical studies and their current and future clinical role, with a special reference to the Nordic healthcare systems. Our considerations are restricted to the most established liquid biopsy specimens: circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Both ctDNA and CTCs have been used for prognostic stratification, treatment choices, and treatment monitoring in solid cancers. Several recent publications also support the role of ctDNA in early cancer detection. ctDNA seems to provide more robust clinically relevant information in general, whereas CTCs have the potential to answer more basic questions related to cancer biology and metastasis. Epidermal growth factor receptor-directed treatment of non-small-cell lung cancer represents a clinical setting where ctDNA already has entered the clinic. The role of liquid biopsies in treatment decisions, standardization of methods, diagnostic performance and the need for further research, as well as cost and regulatory issues were identified as factors that influence further integration in the clinic. In conclusion, substantial evidence supports the clinical utility of liquid biopsies in cancer diagnostics, but further research is still required for a more general application in clinical practice. Full article
(This article belongs to the Special Issue Cancer Testing in the Modern Diagnostic Molecular Pathology Laboratory)
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14 pages, 304 KiB  
Review
Utility of Circulating Tumor DNA in Different Clinical Scenarios of Breast Cancer
by Alexandra Mesquita, José Luís Costa and Fernando Schmitt
Cancers 2020, 12(12), 3797; https://doi.org/10.3390/cancers12123797 - 16 Dec 2020
Cited by 4 | Viewed by 2297
Abstract
Breast cancer is a complex disease whose molecular mechanisms are not completely understood. Developing target therapies is a promising approach. Therefore, understanding the biological behavior of the tumor is a challenge. Tissue biopsy in the metastatic setting remains the standard method for diagnosis. [...] Read more.
Breast cancer is a complex disease whose molecular mechanisms are not completely understood. Developing target therapies is a promising approach. Therefore, understanding the biological behavior of the tumor is a challenge. Tissue biopsy in the metastatic setting remains the standard method for diagnosis. Nevertheless, it has been associated with some disadvantages: It is an invasive procedure, it may not represent tumor heterogeneity, and it does not allow for treatment efficacy to be assessed or early recurrences to be detected. Analysis of circulating tumor DNA (ctDNA) may help to overcome this as it is a non-invasive method of monitoring the disease. In early-stage disease, it can detect early recurrences and monitor tumors’ genomic profiles, identifying the emergence of new genetic alterations which can be related to tumor-acquired resistance. In the metastatic setting, the analysis of ctDNA may also allow for the anticipation of clinical and radiological progression of the disease, selection of targeted therapies, and for a photogram of tumor heterogeneity to be provided. It may also detect disease progression earlier in locally advanced tumors submitted to neoadjuvant treatment, and identify minimal residual disease. ctDNA analysis may guide clinical decision-making in different scenarios, in a precision medicine era, once it acts as a repository of genetic tumor material, allowing for a comprehensive mutation profiling analysis. In this review, we focused on recent advances towards the implementation of ctDNA in a clinical routine for breast cancer. Full article
(This article belongs to the Special Issue Cancer Testing in the Modern Diagnostic Molecular Pathology Laboratory)
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