Advancing Cancer Diagnosis: Integrating Molecular Pathology into Histopathology for Solid Tumors

A special issue of Journal of Molecular Pathology (ISSN 2673-5261).

Deadline for manuscript submissions: closed (31 October 2025) | Viewed by 2612

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Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, Anatomic Pathology, University of Catania, 95123 Catania, Italy
Interests: neuropathology; surgical pathology; uveal melanoma; immunohistochemistry; dermatopathology; oncology
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Special Issue Information

Dear Colleagues, 

The integration of molecular pathology with histopathology is transforming the diagnosis of solid tumors, enhancing precision and paving the way for personalized treatment strategies. Molecular techniques like Next-Generation Sequencing (NGS) allow comprehensive profiling of genetic alterations, while immunohistochemistry (IHC) and multiplex immunofluorescence reveal biomarker expressions essential for therapy selection. Digital pathology and AI offer improved accuracy and efficiency in tissue analysis, while liquid biopsies enable non-invasive monitoring of tumor dynamics. This multidisciplinary approach provides a deeper understanding of tumor biology, enabling tailored interventions for improved patient outcomes.

Dr. Giuseppe Broggi
Guest Editor

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Keywords

  • molecular pathology
  • solid tumors
  • next-generation technologies
  • target treatment
  • digital pathology

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Published Papers (2 papers)

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Research

20 pages, 4910 KB  
Article
Evaluation of Predictive Markers for Immunotherapy in Colorectal Cancer: Concordance Between MMR Protein Expression and Microsatellite Instability in a Retrospective Series
by Giulia Martinelli, Rossella Bruno, Marco Maria Germani, Anello Marcello Poma, Paola Vignali, Chiara Cremolini and Clara Ugolini
J. Mol. Pathol. 2026, 7(1), 9; https://doi.org/10.3390/jmp7010009 - 20 Feb 2026
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Abstract
Background/Objectives: In metastatic colorectal cancer (mCRC) the evaluation of mismatch repair (MMR) and microsatellite instability (MSI) status is essential to identify patients eligible for treatment with immune-checkpoint inhibitors (ICI). This study aims to evaluate the potential utility of Comprehensive Genomic Profiling (CGP) in [...] Read more.
Background/Objectives: In metastatic colorectal cancer (mCRC) the evaluation of mismatch repair (MMR) and microsatellite instability (MSI) status is essential to identify patients eligible for treatment with immune-checkpoint inhibitors (ICI). This study aims to evaluate the potential utility of Comprehensive Genomic Profiling (CGP) in assessing MSI status, in addition to other immunotherapy-predictive biomarkers such as high tumor molecular burden (TMB) and the POLE and POLD1 mutations. Methods: A total of 138 mCRC tumor samples underwent a first-level molecular test (MMR status by immunohistochemistry, MSI by a melting-based PCR approach and RAS/BRAF mutational status by a small next-generation sequencing (NGS) panel) and second-level CGP analysis by the FoundationOne CDx assay. The prevalence of dMMR and MSI tumors was reported. Moreover, the concordance between the MMR and MSI status was determined, and discordant cases were discussed. Results: Twelve cases (8.7%) were MMR-deficient (dMMR); 10 showed high MSI and TMB (>10 mut/Mb). MSI status assessed by CGP and PCR was concordant in all cases except one MSH6-deficient tumor. Two dMMR cases were stable with low TMB. Moreover, in two MLH1/PMS2-deficient cases CGP revealed pathogenic alterations in the MSH2 and MSH6 genes; in both cases, the MLH1 promoter was hypermethylated. A high TMB was the only positive biomarker in 11 cases with a proficient MMR system and no MSI. Conclusions: MSI assessment by CGP analysis showed high concordance (98%) with MMR and was helpful in evaluating ICI eligibility in three out of twelve dMMR cases. Overall, compared to standard methods, analyzing a broader range of microsatellite loci and the simultaneous assessment of multiple predictive biomarkers by CGP may increase diagnostic accuracy and improve therapeutic assessment. Full article
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17 pages, 1004 KB  
Article
Incorporation of Microsatellite Instability and Tumor-Infiltrating Lymphocytes in Opisthorchis viverrini-Associated Cholangiocarcinoma: Predicting Patient Outcomes
by Natcha Khuntikeo, Apiwat Jareanrat, Vasin Thanasukarn, Tharatip Srisuk, Vor Luvira, Watcharin Loilome, Poramate Klanrit, Anchalee Techasen, Jarin Chindaprasirt, Prakasit Sa-Ngiamwibool, Chaiwat Aphivatanasiri, Sureerat Padthaisong, Piya Prajumwongs and Attapol Titapun
J. Mol. Pathol. 2025, 6(4), 30; https://doi.org/10.3390/jmp6040030 - 1 Dec 2025
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Abstract
Background: Cholangiocarcinoma (CCA) has the highest incidence in Northeastern Thailand, where patients generally present with late diagnosis and poor prognosis. Opisthorchis viverrini (OV) infection is the major cause of CCA, with oxidative stress driving DNA mutations and genetic instability. Microsatellite instability (MSI) is [...] Read more.
Background: Cholangiocarcinoma (CCA) has the highest incidence in Northeastern Thailand, where patients generally present with late diagnosis and poor prognosis. Opisthorchis viverrini (OV) infection is the major cause of CCA, with oxidative stress driving DNA mutations and genetic instability. Microsatellite instability (MSI) is a predictive biomarker in several cancers. This study aimed to investigate MSI status and its association with clinicopathological features and survival of CCA patients. Methods: Tissue and serum samples were collected from 25 surgical CCA patients. MSI status and mismatch repair (MMR) proteins were evaluated using an MSI scanner and immunohistochemistry (IHC). Serum OV IgG was assessed by ELISA, while tumor-infiltrating lymphocytes (TILs) were evaluated by two pathologists. Associations of MSI with clinicopathological features, OV status, MMR, and survival were analyzed. Results: Among CCA patients, 66.7% were MSI-high and 33.3% were MSI-low. MSI-high significantly correlated with age < 57 years, intraductal growth pattern, OV positivity, and early-stage disease. Patients with MSI-high and high TILs showed markedly improved median survival compared to MSI-low with low TILs (94.0 vs. 16.8 and 3.0 months; HR = 6.82 and 14.10; p = 0.004 and 0.001). Incorporation of MSI and TILs remained an independent prognostic factor in multivariate analysis (p < 0.05). Conclusions: MSI-high is highly prevalent in OV-associated CCA and is associated with intraductal growth, OV infection, and early-stage disease. Combined MSI and TIL status may serve as an independent prognostic factor, warranting validation in larger cohorts. Full article
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