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Cancers
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Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations
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Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1764

Special Issue Editors

Dr. Paola Parente

E-Mail Website
Guest Editor
Unit of Pathology, Fondazione IRCCS Ospedale “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy
Interests: gastro-intestinal cancer; bilio-pancreatic cancer; IBD; celiac disease; histopathology; immunohistochemistry; hematopathology
Special Issues, Collections and Topics in MDPI journals
Dr. Marco Donatello Delcuratolo

E-Mail Website
Guest Editor
Unit of Oncology, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
Interests: gastrointestinal cancers; lung cancer; target therapy; immunotherapy

Special Issue Information

Dear Colleagues,

The field of cancer pathology in the new era of precision medicine is characterized by a dynamic interplay between morphology and molecular biology, with profound implications for clinical management. Traditional histopathology and immunohistochemical assays are now closely integrated with next-generation sequencing technologies that enable complete genomic profiling. A growing area of focus is investigating the role of the tumor microenvioronment, in particular the role of stroma and immune cells in neoplasia development and response to therapy. This Special Issue, Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations, aims to present a curated selection of original studies and comprehensive reviews that highlight the evolving role of pathology in cancer care. Case reports with unique clinical significance are also welcome. We especially encourage contributions that explore the impact of emerging molecular diagnostics in the fields of genomics and epigenetics and how these innovations contribute to the identification of new therapeutic targets and biomarkers to improve patient outcomes. We anticipate that this Special Issue will provide preclinicians and clinicians with the most up-to-date evidence on the role of oncologic pathology in guiding clinical decision-making across different tumor disease settings.

Dr. Paola Parente
Dr. Marco Donatello Delcuratolo
Guest Editors

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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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

  • solid neoplasia
  • predictive and prognostic biomarkers
  • target therapy
  • tumor microenvironment
  • molecular biology

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Published Papers (3 papers)

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Research

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15 pages, 1511 KB  
Article
Age-Related Multigene Analysis of Colorectal Cancer Using Next-Generation Sequencing
by Monika Kozlowska-Geller, Łukasz Nawacki, Monika Wawszczak-Kasza, Wojciech Lewitowicz, Jacek Bicki and Piotr Lewitowicz
Cancers 2025, 17(24), 3909; https://doi.org/10.3390/cancers17243909 - 6 Dec 2025
Viewed by 166
Abstract
Background: Colorectal cancer (CRC) remains a major global health problem, with rising incidence among younger individuals. The implementation of next-generation sequencing (NGS) has enabled comprehensive multigene analysis to identify cancer-predisposing variants and molecular alterations in tumors. However, data on age-related genetic differences in [...] Read more.
Background: Colorectal cancer (CRC) remains a major global health problem, with rising incidence among younger individuals. The implementation of next-generation sequencing (NGS) has enabled comprehensive multigene analysis to identify cancer-predisposing variants and molecular alterations in tumors. However, data on age-related genetic differences in CRC from Central and Eastern European populations, including Poland, remain limited. Methods: This study aimed to explore molecular differences in CRC between patients aged ≤50 and >50 years in a Polish cohort. Tumor DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 54 treatment-naive patients. Targeted sequencing of hot spot regions of 50 genes with known association to cancer was performed using an AmpliSeq for Illumina Cancer Hotspot Panel v2. Results: Variant frequencies in younger vs. older patients were: TP53 (71.4% vs. 57.6%), APC (57.1% vs. 45.5%), KRAS (28.1% vs. 72.7%), NRAS (28.6% vs. 0%), SMAD4 (9.5% vs. 12.1%), PIK3CA (14.3% vs. 24.2%), and FBXW7 (4.8% vs. 14.7%). Co-occurrence of APC/KRAS/TP53 variants was observed in 20% of cases. KRAS mutations were significantly more frequent in older patients (p-value = 0.001), while NRAS mutations occurred exclusively in younger patients (29% vs. 0%, p = 0.021). Overall, 46% of patients exhibited multiple gene alterations (≥3 mutations). Notably, IDH1 and CTNNB1 variants were found only in patients with better prognosis, whereas TP53 variants were nearly five times more frequent in patients with worse outcomes. Conclusions: Multigene panel sequencing revealed distinct age-related molecular patterns in CRC. Younger patients were more likely to harbor NRAS variants, whereas KRAS alterations predominated in older individuals. These findings underscore the relevance of NGS-based multigene profiling for risk stratification and personalized therapy in colorectal cancer. Full article
(This article belongs to the Special Issue Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations)
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11 pages, 785 KB  
Article
Nevus-Associated and De Novo Melanoma: A Cross-Sectional Study on Prognostic Differences
by Emi Dika, Federico Venturi, Biagio Scotti, Alberto Gualandi, Carlotta Baraldi, Sabina Vaccari, Sebastiano Posenato, Corrado Zengarini, Aurora Alessandrini, Leonardo Veneziano, Marco Ardigò and Elisabetta Magnaterra
Cancers 2025, 17(23), 3859; https://doi.org/10.3390/cancers17233859 - 30 Nov 2025
Viewed by 205
Abstract
Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo [...] Read more.
Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo melanoma (DNM) in a large single-center cohort. Methods: We retrospectively analyzed 378 patients with invasive melanoma diagnosed between 2007 and 2021 at a tertiary referral center. Tumors were classified as NAM when histopathologic continuity with a nevus was present, and as DNM otherwise. Clinical, histologic, and prognostic variables were compared using univariate and multivariate analyses. Results: Of 378 melanomas, 90 (24%) were NAM and 288 (76%) were DNM. Patients with NAM were slightly younger (mean 52 vs. 54 years) and more often presented with tumors on the trunk (65.6% vs. 51.7%). NAMs exhibited lower Breslow thickness (0.55 vs. 0.84 mm), reduced mitotic activity (0.17 vs. 1.21/mm2), and less frequent ulceration (2.2% vs. 9.4%). Distant metastases occurred only in DNM (6.6%). Sentinel lymph node positivity (1.1% vs. 6.3%) and melanoma-specific mortality (0% vs. 0.69%) did not differ significantly. Multivariate analysis identified Breslow thickness and mitotic rate as independent predictors of subtype. Conclusions: NAMs present with more favorable histopathologic features than DNMs, yet long-term outcomes appear similar. These findings support divergent pathways of melanoma development and underscore the need for molecular and imaging studies to refine risk stratification and guide management. Full article
(This article belongs to the Special Issue Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations)
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Review

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33 pages, 2286 KB  
Review
Antigenic Dark Matter: Unexplored Post-Translational Modifications of Tumor-Associated and Tumor-Specific Antigens in Pancreatic Cancer
by Amin Safa, Idris Vruzhaj, Marta Gambirasi and Giuseppe Toffoli
Cancers 2025, 17(21), 3506; https://doi.org/10.3390/cancers17213506 - 30 Oct 2025
Viewed by 1098
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits marked resistance to immunotherapy. Beyond its characteristically low tumor mutational burden, post-translational modifications (PTMs) remodel the immunopeptidome and promote immune escape through reversible, enzyme-driven programs. Subject Matter: We synthesize evidence that aberrant glycosylation, O-GlcNAcylation, phosphorylation, and citrullination [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits marked resistance to immunotherapy. Beyond its characteristically low tumor mutational burden, post-translational modifications (PTMs) remodel the immunopeptidome and promote immune escape through reversible, enzyme-driven programs. Subject Matter: We synthesize evidence that aberrant glycosylation, O-GlcNAcylation, phosphorylation, and citrullination constitute core determinants of antigen visibility operating within spatially discrete tumor niches and a desmoplastic stroma. In hypoxic regions, HIF-linked hexosamine metabolism and OGT activity stabilize immune checkpoints and attenuate antigen processing; at tumor margins, sialylated mucins engage inhibitory Siglec receptors on innate and adaptive lymphocytes; within the stroma, PAD4-dependent NET formation enforces T cell exclusion. We also delineate technical barriers to discovering PTM antigens labile chemistry, low stoichiometry, and method-embedded biases and outline practical solutions: ETD/EThcD/AI-ETD fragmentation, PTM-aware database searching and machine-learning models, and autologous validation in patient-derived organoid–T cell co-cultures. Finally, we highlight therapeutic strategies that either immunize against PTM neoepitopes or inhibit PTM machinery (e.g., PAD4, OGT, ST6GAL1), with stromal remodeling as an enabling adjunct. Conclusions: PTM biology, spatial omics, and patient sample models can uncover targetable niches and speed up PDAC vaccination, TCR, and enzyme-directed treatment development. Full article
(This article belongs to the Special Issue Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations)
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