Journal of Pathology and Translational Medicine

Original Articles

Development of a prognostic prediction model for tumor recurrence or progression in gastrointestinal stromal tumors: integrating inflammatory blood indices with 5 mm² versus 50 high-power field mitotic counts: Waratchaya Tirasarnvong, Thammasin Ingviya, Paramee Thongsuksai; J Pathol Transl Med. 2026;60(5):527-538. Published online July 31, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.15

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Abstract PDF Supplementary Material: Background
The behavior of gastrointestinal stromal tumors varies according to tumor size, location, mitotic rate, and rupture. Traditional mitotic counting in 50 high-power fields (HPF; 5.3 mm2) may overestimate progression risk, as 5 mm2 corresponds to 20–25 HPF under modern microscopy. However, the 50-HPF method remains widely used. This study evaluated the impact of two mitotic counting methods on risk classification and developed a prognostic model combining inflammatory biomarkers with clinicopathological factors. Methods: We retrospectively analyzed 150 patients who underwent resection at Songklanagarind Hospital between 2009 and 2021. Patients who had received neoadjuvant therapy or had a second primary cancer were excluded. Mitosis was evaluated using both methods. Clinicopathological and serum biomarker data were collected. The primary outcome was 5-year disease-free or progression-free survival. The model was developed using forward stepwise variable selection based on the time-dependent area under the curve and internally validated by bootstrapping. Results: The 50-HPF method overestimated the Armed Forces Institute of Pathology classification in 14.2% of cases. A model incorporating tumor size, location, rupture, mitotic count within 5 mm2, and systemic immune-inflammation index achieved the highest area under the curve of 0.939 in both training and validation sets, outperforming previous models. The 5-mm2 method demonstrated superior performance to the 50-HPF method across all models (0.939 vs. 0.919 for the proposed model). Conclusions: Mitotic counting in 50 HPF overestimated risk classification in certain cases. Incorporating systemic immune-inflammation index and using a 5 mm2 mitotic count enhanced prognostic model performance.

Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma: Konstantinos Christofidis, Rodanthi Fioretzaki, Stylianos Mavropoulos Papoudas, Nikolaos Charalampakis, Nikolaos Kavantzas, Dimitrios Schizas, Stratigoula Sakellariou; J Pathol Transl Med. 2026;60(2):263-279. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.20

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Abstract PDF Supplementary Material: Background
Gastric adenocarcinoma is a major cause of cancer mortality worldwide, and reliable biomarkers remain insufficient. This study investigates the immunohistochemical expression of progastrin (hPG) and annexin A2 (ANXA2) and the polarization of tumor-associated macrophages in gastric adenocarcinoma to explore their potential prognostic and biological significance. Methods: A retrospective analysis was conducted on formalin-fixed, paraffin-embedded tissue samples from 60 patients with gastric adenocarcinoma (primary tumors, lymph node metastases, and non-tumoral gastric mucosa) and gastric biopsies from 23 healthy controls. The expression of hPG and ANXA2 was quantified using the H-score, and the CD163/human leukocyte antigen–DR (HLA-DR) ratio was used to represent macrophage polarization (M2/M1). Statistical analyses included non-parametric tests, Spearman correlations, Kaplan-Meier survival curves, and Cox proportional-hazards models. Results: ANXA2 expression was significantly elevated in cancer cells from primary tumors and lymph node metastases, compared with the non-tumoral gastric mucosa tissues and gastric mucosa tissues from healthy controls. ANXA2 expression increased with the tumor grade. High ANXA2 levels were associated with shorter overall and disease-free survival, but they did not have independent prognostic value. Although hPG expression correlated positively with ANXA2, it showed no significant prognostic association. The CD163/HLA-DR ratio increased with tumor progression and negatively correlated with ANXA2, but it did not influence survival outcomes. Conclusions: This study is the first to demonstrate the adverse prognostic impact of ANXA2 overexpression in gastric adenocarcinoma tissues from Caucasian patients. Our results suggest that ANXA2 might have utility as a prognostic biomarker and therapeutic target, if further large-scale studies validate and expand our findings.

AMACR is a highly sensitive and specific immunohistochemical marker for diagnosing prostate cancer on biopsy: a systematic review and meta-analysis: Johannes Cansius Prihadi, Stevan Kristian Lionardi, Nicolas Daniel Widjanarko, Steven Alvianto, Fransiskus Xaverius Rinaldi, Archie Fontana Iskandar; J Pathol Transl Med. 2025;59(4):235-248. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.16

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Abstract PDF Supplementary Material

Background
Alpha-methylacyl-CoA racemase (AMACR) is the preferred biomarker for distinguishing malignant from benign glands in prostate biopsies, showing high sensitivity and specificity for prostate cancer. A meta-analysis of immunohistochemistry (IHC) for AMACR is essential to further assess its diagnostic accuracy across diverse sample sources. Methods: A systematic search of databases including MEDLINE, ScienceDirect, ProQuest, Google Scholar, and the Cochrane Library was performed, focusing on studies of AMACR to diagnose prostate cancer, particularly in biopsy samples analyzed through IHC over the last 20 years. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, followed by a meta-analysis of regions and subgroups to calculate summary estimates of diagnostic test accuracy. Results: In the final analysis, 37 studies, with a pooled size of 5,898 samples, were included from the examination of 94 full-text papers. Among them, 27 studies with similar sample sources and testing methodologies underwent meta-analysis, yielding a combined sensitivity estimate of 0.90 (95% confidence interval [CI], 0.86 to 0.93) and specificity of 0.91 (95% CI, 0.83 to 0.95), both with significant heterogeneity (p < .01). The region beneath the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93 to 0.97), positive likelihood ratio was 9.6 (95% CI, 5.3 to 17.4), negative likelihood ratio was 0.11 (95% CI, 0.08 to 0.15), and diagnostic odds ratio was 88 (95% CI, 42 to 181). Conclusions: Our meta-analysis findings substantiate AMACR as a highly accurate tool for diagnosing prostate cancer, specifically in biopsy samples, via immunohistochemical staining. Further studies involving diverse samples are needed to enhance our understanding of the AMACR diagnostic accuracy in a range of clinical settings.

Citations

Citations to this article as recorded by

ATP binding cassette subfamily D member 1: A highly sensitive diagnostic marker for solid pseudopapillary neoplasm of pancreas in biopsy samples——A multi-institutional study
Yuanhao Liu, Junya Peng, Ruizhe He, Xiaowei Xue, Jie Cui, Mengjie Li, Ying-ao Liu, Wanni Xu, Xiaohong Gao, Yingmei Wang, Zhe Zhang, Haizhen Lu, Zhigang Song, Peizhen Hu, Yupei Zhao, Wenze Wang
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Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer
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Cancer and Metastasis Reviews.2026;[Epub] CrossRef
Phenotype-Oriented Characterization of NSC828786 Identifies Convergent HPN-AMACR-Associated Transcriptomic Signatures in Prostate Adenocarcinoma and Broad-Spectrum Antiproliferative Activity
Ya-Ting Wen, Rosario Trijuliamos Manalu, Han-Lin Hsu, Yu-Cheng Kuo, Ruey-Shyang Soong, Feng-Cheng Liu, Maryam Rachmawati Sumitra, Sheng-Liang Huang, Shih-Yu Lee, Sung-Ling Tang, I-Chuan Yen, Hong-Jaan Wang, Bashir Lawal, Alexander T. H. Wu, Hsu-Shan Huang
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Sub-Saharan African Prostate Cancer Patient-Derived Cell Lines and High-Throughput Drug Screening: Addressing Ancestry Underrepresentation in Oncobiology Research
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Prostate Cancer with Pleural Metastasis: A Case Report
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Pathology-Guided Transcriptomic Profiling of Prostate Cancer Identifies Grade-Associated Proliferative and Immune Signatures in a MENA Cohort
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Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics
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Reviews

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer: Uiju Cho, Soyoung Im, Hyung Soon Park; J Pathol Transl Med. 2024;58(2):49-58. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.31

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Abstract PDF

Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

Citations

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Prognostic Value of the Lung Immune Prognostic Index in Advanced Non-Small Cell Lung Cancer Treated with Nivolumab: A Real-World Analysis Beyond PD-L1 Expression
Alperen Akansel Çağlar, Aykut Özmen, Tuğrul Burak Genç, Anıl Yıldız, Özde Melisa Celayir, Shamkal Safarov, Yunus Avcı, Gökmen Umut Erdem, Nilüfer Bulut
Diagnostics.2026; 16(18): 2890. CrossRef
Machine learning methods for histopathological image analysis: Updates in 2024
Daisuke Komura, Mieko Ochi, Shumpei Ishikawa
Computational and Structural Biotechnology Journal.2025; 27: 383. CrossRef
Beyond single biomarkers: multi-omics strategies to predict immunotherapy outcomes in blood cancers
Mohammad Pirouzbakht, Soroosh Hamzeh, Hamed Soleimani Samarkhazan
Clinical and Experimental Medicine.2025;[Epub] CrossRef
Temporal changes in tongue color during immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer: a prospective observational study using digital tongue diagnosis
Eunbyul Cho, Woosu Choi, Jun Hyeok Lim, Ji Woong Son, Seung Hun Jang, Seung Hyeun Lee, Jong Gwon Choi, In-Jae Oh, Tae-Won Jang, Seong Hoon Yoon, Seung Joon Kim, Chang-Min Choi, Sung Yong Lee, Mi Mi Ko, Mi-Kyung Jeong
Oncology Reviews.2025;[Epub] CrossRef

Biomarker testing of cytology specimens in personalized medicine for lung cancer patients: Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(6):326-333. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.17

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Abstract PDF

Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

Citations

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Concordance study of bronchial biopsy tissues and matched bronchial brushing cytology specimens in driver gene detection of non-small cell lung cancer
Xiongfeng Li, Lexia Chen, Peijia Niu, Jing Wang, Xupeng Sun, Ning Lu, Yahan Weng
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Cancer Cytopathology.2024; 132(9): 547. CrossRef
Best-Practice Biomarker Testing of Oesophago-Gastric Cancer in the UK: Expert Consensus Recommendations Developed Using a Modified Delphi
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Current status and future perspectives of liquid biopsy in non-small cell lung cancer: Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim; J Pathol Transl Med. 2020;54(3):204-212. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.27

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Abstract PDF

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

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