Pathology & Oncology Research最新文献

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Despite advances in various treatment approaches, outcomes for patients with metastatic CRC (mCRC) remain poor, and treatment-associated side effects significantly impact quality of life. While immunotherapy has shown promise in certain malignancies, its efficacy in CRC is limited to a minority of patients, highlighting the urgent need for novel therapeutic targets to improve treatment efficacy while minimizing off-target effects. B7-H3 (CD276) has emerged as a promising immunotherapeutic target due to its selective expression on tumor cells and neovasculature, with minimal presence in healthy tissues. A novel IgG-based bispecific antibody targeting B7-H3 and CD3, CC-3, has demonstrated strong preclinical efficacy in stimulating T cell-mediated antitumor responses and is currently being evaluated in a first-in-human trial including patients with mCRC (NCT05999396). In this study, we investigated B7-H3 expression in a cohort of n = 55 mCRC patients and assessed its correlation with demographic, pathological, and molecular factors, as well as clinical outcomes. Additionally, to evaluate the stability of B7-H3 expression over time, we analyzed sequential biopsies from metastatic lesions from n = 7 patients at subsequent time points. Our findings demonstrate that B7-H3 is consistently overexpressed in mCRC, independent of demographic factors, primary tumor localization (right vs. left colon), common molecular and genetic alterations (HER2, MSI, KRAS, NRAS, BRAF, PIK3CA, p53), and serum tumor markers. Longitudinal analysis showed that B7-H3 expression was comparable or increased over time in sequential metastatic specimens. No significant association was observed between B7-H3 expression and overall survival or progression-free survival, and prior chemotherapy treatment did not influence B7-H3 expression levels. In conclusion, B7-H3 is stably and ubiquitously expressed in mCRC, reinforcing its potential as a robust target for immunotherapeutic strategies, including bispecific antibodies. The lack of variability across patient subgroups suggests that routine pre-treatment assessment of B7-H3 may not be necessary. These findings provide a strong rationale for the continued clinical evaluation of B7-H3-targeted therapies, such as CC-3 (NCT05999396), in mCRC patients.

Conjunctival melanoma (CoM) is a rare and aggressive ocular surface malignancy, characterised by increasing incidence, clinical complexity, and substantial challenges in diagnosis and treatment. This review consolidates current knowledge on epidemiology, clinical presentation, genetic and epigenetic foundations, molecular mechanisms, emerging therapeutic strategies, and prognostic factors for localised and metastatic CoM. CoM exhibits distinct biological behaviours, sharing molecular traits with cutaneous and mucosal melanomas, while significantly diverging from uveal melanoma. Key genetic alterations include mutations in BRAF, NF1, and PTEN, elevated mTOR expression, and specific miRNA profiles, which influence tumour progression and response to therapy. Recent advances in treatment, especially immune checkpoint inhibitors such as CTLA-4 and PD-1 receptor inhibitors, along with targeted therapies like BRAF and MEK inhibitors, have led to marked improvements in outcomes for advanced cases. Emerging strategies, including dendritic cell vaccines and epigenetic therapies, hold considerable promise in addressing ongoing clinical challenges. This review integrates case studies and clinical research to demonstrate the practical application of these therapies, highlighting their efficacy and limitations. Combining clinical expertise, genetic insights, and the latest therapeutic developments, offers a comprehensive overview of CoM, underscoring the critical role of a multidisciplinary approach in optimising diagnosis, management, and prognosis to improve patient outcomes.

Purpose: Traditional markers have various limitations in recognizing the breast origin of distant metastatic breast carcinoma (DMBC), especially in ER-negative or low expression cases. In recent years, TRPS1 has been reported as a breast marker with satisfactory sensitivity and specificity in triple-negative breast cancers (TNBC). We aimed to compare the expression of TRPS1, GATA3, and GCDFP-15 in ER-negative or low-ER-expressing DMBC, and to further evaluate the diagnostic value of TRPS1.

Methods: Immunohistochemical staining for TRPS1, GATA3, and GCDFP-15 was performed in 107 cases of ER-negative or low expression DMBC specimens. Nuclear staining was considered positive for TRPS1 and GATA3, and cytoplasmic staining was considered positive for GCDFP-15.

Results: The positive rates for TRPS1, GATA3, and GCDFP-15 were 90.65% (97/107), 91.59% (98/107), and 42.99% (46/107), respectively. There was no significant difference in the expression rate and intensity between the first two markers (p = 0.929), but both rates were significantly higher than that of GCDFP-15 (p < 0.05). Among these, 6 cases showed positive expression for TRPS1 while GATA3 and GCDFP-15 were negative; 8 cases showed positive expression for GATA3 while TRPS1 and GCDFP-15 were negative.

Conclusion: TRPS1 is as effective as GATA3 in confirming breast origin for ER-negative or low expression DMBC, and the two markers exhibit excellent complementary effects, both outperforming GCDFP-15. The combined application of TRPS1 and GATA3 is the optimal method to confirm that ER-negative or low-expression distant metastatic carcinoma originates from the breast.

This study provides a comprehensive analysis of early-stage resectable non-small cell lung cancer (NSCLC) in Hungary, investigating incidence rates, demographic trends, treatment patterns and survival outcomes. We used data from the National Health Insurance Fund (NHIF) spanning 2013-2022, and we analyzed 6,571 patients with available NSCLC histology and no metastasis, who underwent curative surgery within 6 months of diagnosis, and evaluated epidemiological trends and the use of neoadjuvant and adjuvant therapies. For the efficacy analysis, we narrowed the patient cohort to 5,494 patients diagnosed and treated between 2013 and 2019 with at least three-year follow-up data. Key endpoints included overall survival (OS) and disease-free survival (DFS), inferred via time to first subsequent therapy (TFST). Our results revealed a gradual decline in early-stage resectable NSCLC diagnoses, with a significant drop in 2020, likely linked to COVID-19 restrictions. Older age groups (66-75 years) represented a growing proportion of cases, reflecting shifting demographic trends. Among patients with EGFR mutations receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, OS significantly improved compared to those not receiving EGFR-TKI therapy, who are assumed to have wild-type EGFR status (HR = 0.58 (95% CI: 0.47-0.72), p < 0.0001). These findings underscore the importance of early detection, comprehensive biomarker testing and targeted therapies in improving outcomes for resectable NSCLC patients. Future studies with extended follow-up and integration of broader clinical data, including staging and patient comorbidities, are warranted to optimize therapeutic strategies.

Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. However, the combined clinical and biological scores commonly used to predict the clinical outcome are imperfect and need improvement. The main goal of our study was to assess the effect of mtDNA genetics on the prognosis of ccRCC patients and to explore morphologic correlation. Mitochondrial DNA copy number (mtDNAcn) variation between tumor and paired matched healthy kidney tissue was assessed by real-time quantitative PCR and expressed as a ratio in 105 patients. According to this median ratio, the cohort was divided into two groups: "LOW" (n = 53) and "HIGH" (n = 52). Cancer-Specific Survival (CSS) and Disease-Free Survival were assessed in each group. The tumor samples were classified into two subtypes (Clear or Eosinophilic cells) according to the cytoplasmic morphology. CSS was significantly reduced in the "HIGH" than in the "LOW" group with respective 5-year survival rates: 78.7% (CI 95: 64.8-95.5) and 95.5% (CI 95 87.1-100.0) (Hazard Ratio: 7.4 (CI 95: 1.9-29.9, p = 0.027*) in multivariate analysis, including pathological classification, tumor size, International Society of Urological Pathology grade, lymphovascular invasion, dedifferentiated pattern, necrosis and adjuvant therapy. Next-generation sequencing of mtDNA was performed on 14 tumors and matched healthy kidney tissue. No hotspot mutation or redundant large deletion was found. None of the variants or large deletions identified had an impact on prognosis. MtDNAcn variation in tumor relative to normal kidney appears as an independent prognostic factor in ccRCC, which was also associated with eosinophilic morphology. MtDNA content could be considered an additional prognostic factor, in combination with other predictive parameters. Furthermore, these results underline the importance of the role of mitochondria in ccRCC and the need for further functional studies to understand the pathophysiological mechanisms better and consider therapies targeting mitochondrial metabolism.

Background: Fundic gland tumors are a rare subtype of gastric tumors with fundic gland differentiation. This group of tumors has a low incidence rate and shows indistinctive cellular atypia, obvious structural atypia, special tissue morphology, and clinical prognosis, thus leading to diagnostic challenges.

Aim: We aimed to investigate the clinical and endoscopic characteristics and pathological features of gastric adenocarcinoma of the fundic gland (GA-FG) to provide a better understanding of this disease.

Methods: We collected data from patients diagnosed as having GA-FG at Guangdong Provincial People's Hospital between January 2019 and April 2024. The analysis focused on their clinical data, endoscopic characteristics, pathological morphological characteristics, immunohistochemistry results, treatment, and prognosis.

Results: Among the four patients were two men and two women (age range, 52-65 years). The tumors were mainly located in the gastric fundus and gastric body, and the lesions commonly had a superficial bulge. Three patients had an initial diagnosis of oxyntic gland adenoma, which was diagnosed as GA-FG after complete resection. These tumors were negative for MUC5AC, but showed diffuse strong positivity for MUC6 and pepsinogen I, and synaptophysin expression.

Conclusion: GA-FG is a rare gastric tumor with unique morphological features. As it is difficult to diagnose with a biopsy, immunohistochemistry plays an important role in the differential diagnosis. Oxyntic gland adenoma can be regarded as the intramucosal stage of GA-FG. Although all patients were negative for MUC5AC expression, MUC6 and pepsinogen I can help the diagnosis of GA-FG.

This case study delves into the link, between exposure to Bisphenol A (BPA) and kidney issues filling a gap in human focused research found in studies. The individual, a 72-year man with a history of BPA exposure in a plastics manufacturing facility experienced a gradual decline in kidney function over 18 months. Medical tests showed kidney disease with a buildup of lipofuscin in renal tubular cells upon examination. This discovery suggests a connection between BPA exposure and kidney damage underscoring the need for investigation. The lack of human based evidence highlights the importance of research to understand the toxic effects of BPA on the kidneys. In addition, to its implications this case emphasizes the importance of improving safety protocols and raising awareness among healthcare professionals in relevant work environments to reduce potential health risks associated with BPA exposure.

Many subtypes of bone and soft tissue tumours harbour specific chromosome translocations leading to chimeric fusion genes. The identification of these specific fusion genes is the basis of molecular diagnoses in such tumours. Break-apart FISH is a robust method that is commonly used to identify these translocations and provide diagnostic support to histological interpretations. The signal patterns of the break-apart probes are usually easily interpreted. However, some cases show abnormal signal patterns leading to equivocal and challenging interpretation. The incidence of these abnormal patterns is largely unknown. Using a retrospective cohort we explored the incidence of abnormal signal patterns across common bone and soft tissue tumour types to raise awareness of this occurrence and to aid in the interpretation. In total, 1,087 bone and soft tissue tumours tested by break-apart probes were examined. The abnormal signal patterns were classified as deletion, additional copy and amplification, which were found at highest frequency in low-grade fibromyxoid sarcoma (32%, 6/19), and at moderate frequencies in those from alveolar rhabdomyosarcoma (10%, 9/94), nodular fasciitis (9%, 18/209), synovial sarcoma (8%, 17/207) and Ewing sarcoma/round cell sarcoma with EWSR1-non-ETS fusions (6%, 29/497). The lowest frequency was found in clear cell sarcoma (1%, 1/61). Despite the equivocal results from the abnormal signal patterns, the specific fusion genes were confirmed by orthogonal molecular techniques such as FISH with fusion probes, RT-PCR or next-generation sequencing.

Background: Benign fibro-osseous lesions are characterized by the replacement of normal bone with cellular fibrous connective tissue with new bone formation. The published cytogenetic information on these tumors is limited to only few cases. Here, we report the cytogenetic and molecular genetic findings of a fibro-osseous tumor.

Methods: A fibro-osseous lesion was investigated for genetic abnormalities using banding cytogenetics, fluorescence in situ hybridization (FISH), RNA sequencing, and direct cycle Sanger sequencing.

Results: The karyotype was 46,XX,t(4;11;14;12)(q35;p15;q22;q13)[7]/46,XX [3], with no rearrangement of HMGA2. RNA sequencing revealed two FRMD6::PTH chimeric transcripts, originating from the fusion point 14q22;11p15 of the t(4;11;14;12). In these transcripts, exon 1 of FRMD6 fused to either exon 1 or exon 2 of PTH. Direct cycle sequencing confirmed the presence of these FRMD6::PTH chimeric transcripts.

Conclusion: This study reports, for the first time, the presence of the FRMD6::PTH chimera in fibro-osseous tumor. In this chimera the expression of the entire coding region of PTH is regulated by the ubiquitously expressed FRMD6 gene promoter. Dysregulation of PTH expression may have significant implications for processes regulated by PTH protein.

Objective: This study aimed to assess the likelihood of detecting cancer in final pathology and evaluate the accuracy of intraoperative frozen-section assessment in cases of endometrioid intraepithelial neoplasia (EIN).

Material and methods: We included patients diagnosed with EIN at Hacettepe University Hospital who subsequently underwent hysterectomy at the same center between January 2011 and March 2023. EIN diagnoses made at other institutions were re-evaluated and confirmed by co-author gynecopathologists.

Results: A total of 354 patients diagnosed with EIN underwent hysterectomy. The majority of patients (68.5%) had a final diagnosis of EIN. Endometrial cancer (EC) was identified in 11.3% (n = 40) of patients in the final pathology. Advanced age (≥50 years) (OR = 2.52; 95% CI: [1.27-4.96]; p = 0.006) and menopausal status (OR = 2.62; 95% CI: [1.34-5.11]; p = 0.004) were significantly associated with an increased risk of EC. Among 263 patients who underwent intraoperative frozen-section assessment, EC was detected in 12.9% (n = 34). The sensitivity and specificity of frozen-section assessment for EC detection were 41.1% and 100%, respectively. The frozen-section assessment failed to identify only one of the seven patients who required staging surgery.

Conclusion: Our study demonstrates that a preoperative EIN diagnosis carries an 11.3% risk of concurrent EC. Additionally, the likelihood of EC is significantly higher in older and postmenopausal patients. The majority of patients requiring staging surgery were identified by frozen-section assessment. Our findings indicate that frozen-section assessment provides the necessary information for adequate surgical treatment in EIN cases.