Pathology & Oncology Research最新文献

Purpose: Valosin-containing protein (VCP/p97) is a key regulator of proteostasis and cellular stress response and has been linked to tumor progression and poor prognosis in various malignant diseases. However, data on its role in laryngeal squamous cell carcinoma (LSCC) are lacking.

Methods: In this retrospective single-center study, VCP/p97 protein expression was analyzed by immunohistochemistry in a cohort of 100 LSCC patients. Expression levels were semi-quantitatively assessed with H-Score, compared to normal tissue if possible and correlated with clinicopathological parameters. Survival analyses were evaluated by Cox regression.

Results: VCP/p97 was expressed in all tumors. Most LSCC (77.0%) showed a uniform staining pattern. 46 of these tumors (59.7%) exhibited a staining intensity of 2-3. Among the tumors with a non-homogeneous staining pattern (n = 23), two tumors showed a predominance to lower staining (staining intensity 1). In 13 samples a comparison to normal epithelium was possible. In these samples, 9 (69.2%) samples showed higher VCP/p97 expression compared to the normal epithelium and 4 (30.8%) showed lower expression. VCP/p97 H-Score was not significantly associated with tumor stage, grade, lymph node status or patient survival.

Conclusion: Although VCP/p97 expression is not prognostic in LSCC, its consistent expression may suggest a potential role as a molecular target. Further functional and translational studies are warranted to explore the therapeutic utility of VCP/p97 inhibition in LSCC.

Objective: To evaluate the technical performance and clinical integration of FoundationOne®CDx (F1CDx) for high-grade serous ovarian cancer (HGSOC), focusing on its role in guiding PARP inhibitor (PARPi) therapy recommendations in a tertiary oncology center.

Methods: We conducted a retrospective analysis of 178 F1CDx tests performed on 168 HGSOC patients with unknown BRCA mutation status between January 2019 and August 2024. Molecular findings, including BRCA1/2 mutations, homologous recombination deficiency (HRD) status, loss of heterozygosity (LOH) scores, and HRR-related gene alterations, were correlated with tumor board recommendations and decisions for PARPi therapy. Laboratory turnaround time (TAT), assay performance, and integration into clinical workflows were assessed.

Results: The F1CDx assay successfully generated comprehensive molecular profiles in 174 samples, with minimal limitations due to computational tumor content or inconclusive HRD readout. BRCA1/2 mutations were detected in 13.1% of patients, and 39.5% of tumors were HRD-positive (LOH ≥16%). In the internal cohort, 81.8% of patients received PARPi therapy recommendations, all directly informed by F1CDx results. PARPi selection differed by HRD status, with niraparib favored in HR-proficient and olaparib in HRD-positive tumors. The mean laboratory TAT was 8.4 days (standard deviation ±3.8), with 92.2% of tests completed within 14 days. No additional profiling was required for PARPi therapy recommendation, and no incidental findings beyond the scope of HRD testing were detected.

Conclusion: Molecular profiling with F1CDx proved to be a technically feasible, clinically impactful, and time-efficient assay, demonstrating its value in supporting molecular-guided PARPi therapy recommendations in the routine care of HGSOC patients.

Introduction: The antibody-drug conjugate (ADC) Sacituzumab-Govitecan (SG), a humanized anti-Trop2 monoclonal antibody linked to the cytotoxic topoisomerase I inhibitor SN38, achieved promising results in the treatment of various solid tumors. Treatment approaches with SG requires the expression of Trop2 within tumor cells. The present study explored immunohistochemical Trop2 expression in cervical carcinomas in correlation with histologic subtypes and p16 expression status.

Material and methods: Using an immunoreactive score (IRS), immunohistochemical Trop2 expression in surgically treated cervical carcinoma specimens was evaluated by comparing squamous cell carcinomas and adenocarcinomas, and the expression status of p16 as a surrogate marker for high-risk HPV infection.

Results: A total of 101 cases were included in this study. Of these 75% were squamous cell carcinomas, and 25% were adenocarcinomas, and 5% showed negative immunoexpression for p16, indicating HPV-independent carcinoma. All tumors showed at least weak Trop2 expression. There were no differences in the mean Trop2 IRS-scores comparing histological subtype [squamous: 8.5 (3-9) vs. adeno: 6 (1-9); p = 0.8] and p16 expression status [positive: 9 (6-9) vs. negative: 8 (6-9; p = 0.6]. No differences in Trop2 expression were observed when post-surgical tumor stage, pelvic lymph node status and peritumoral stromal remodelling (desmoplastic response and peritumoral infiltrating lymphocytes) were analysed.

Conclusion: Regardless of the histologic tumor type and p16 expression status, cervical carcinomas show high Trop2 expression and, therefore, may represent a promising therapeutic target. Clinical trials exploring Trop2 directed ADCs such as Sacituzumab-Govitecan are warranted in this cancer type, including the prognostically poor HPV-independent (p16 negative) tumors, mainly adenocarcinomas.

Significance: Regardless of the histologic tumor type and p16-expression status, cervical carcinomas show high Trop2 expression, which may therefore represent a promising therapeutic target in these tumors.

Objective: Histopathological growth patterns (HGPs) were identified as prognostic factors for colorectal adenocarcinomas; however, they have been examined in a consecutive setting with controversial results. Our study aimed to examine HGPs' association with clinicopathological factors in a retrospective, consecutive, single-center, cohort study.

Methods: Our study comprised the data of patients who were treated for liver metastases from 2011 to 2023. In all cases, general clinicopathological data were registered. The histological slides of all metastatic foci were individually evaluated. Statistical analyses were carried out by using the Kruskal-Wallis and Fisher's exact test. P-values less than 0.05 were considered significant.

Results: Altogether 336 liver metastases from 205 patients have been included in our retrospective, consecutive, single-center, cohort study. The male-to-female ratio was 116:89, and the average age of patients was 68 years (median: 69.5; range: 27-93). Most examined cases were of colorectal origin (n = 164). Replacement pattern was found to be the most common (n = 99). The 163 colorectal adenocarcinoma metastasis cases reflected a similar order of magnitude of replacement type (n = 78) and desmoplastic (n = 68) HGPs. The majority (70%) of neuroendocrine tumours (n = 10) showed pushing HGP, while 3 of 5 non-epithelial tumours were associated with replacement-type HGP. A significant association was found between HGPs and histological subtype (p < 0.001), grade (p = 0.002), the presence of venous spread (p = 0.02), and the largest diameter of liver metastasis (p = 0.023).

Conclusion: Even though our study highlights the HGPs' association with several clinicopathological parameters that might influence prognosis, their role in the treatment process of colorectal or other carcinomas remains controversial.

Objective: We analyzed changes in intratumoral CD8⁺ and CD4⁺ T-cell subpopulations following neoadjuvant chemoimmunotherapy in non-small cell lung cancer. We then assessed whether these alterations favored better outcomes and explored their association with the tumor microenvironment.

Methods: Paired pre- and post-treatment samples from 32 patients with non-small cell lung cancer who underwent neoadjuvant chemoimmunotherapy at Shandong Cancer Hospital (January 2021-June 2023) were analyzed retrospectively. A quantitative analysis of tumor cells and their microenvironment was performed using a tissue microarray and a multiplex immunofluorescence technique. The analysis was based on the number of cells per thousand nucleated cells. Patients exhibiting a major pathologic response were classified as responders. The delta parameter (post-treatment minus pre-treatment) was utilized to assess changes in these indicators, and associations with treatment response were identified using the Wilcoxon Signed-Rank test and logistic regression analyses.

Results: Of the 32 patients, 59.38% were classified as responders. Across all patients, neoadjuvant chemoimmunotherapy significantly reduced the densities of dysfunctional CD8⁺ resident memory T cells and cytotoxic and dysfunctional CD8⁺ bystander T cells, while conventional CD4⁺ T cells increased significantly. Similar trends were observed in the response group. In the non-response group, only cytotoxic CD8⁺ bystander T cells were reduced in number. Logistic regression analysis revealed that a high delta conventional CD4⁺ T cells is more favorable for MPR (OR = 0.13, p = 0.038), exhibiting a similar trend to changes in HIF-1α (p = 0.049).

Conclusion: Alterations in specific CD8⁺ and CD4⁺ T-cell subpopulations during neoadjuvant chemoimmunotherapy may favor better outcomes and are potentially associated with tumor hypoxia. These findings provide a new perspective on developing strategies to improve treatment sensitivity in non-small cell lung cancer.

Testicular germ cell tumors (TGCTs), though typically responsive to therapy, may rarely develop somatic-type malignancy (STM), a transformation associated with poor prognosis and chemoresistance. This study presents two cases of postpubertal-type teratoma with intestinal-type adenocarcinoma as STM, offering insights into their clinical, histopathological, immunophenotypic, and molecular profiles. The first patient, a 63-year-old male, presented with pulmonary and retroperitoneal metastases and underwent orchiectomy, revealing an intratesticular intestinal-type adenocarcinoma. Molecular testing confirmed 12p overrepresentation and pathogenic mutations in CTNNB1, STK11, and MDM2. The second patient, initially diagnosed at age 35 with a mixed TGCT, developed STM as a late recurrence 16 years post-orchiectomy, manifesting as a retroperitoneal mass with vertebral invasion. Histology again confirmed intestinal-type adenocarcinoma, and molecular testing revealed amplification of ERBB2, KRAS, along with mutations in TP53 and PIK3CA. Both cases were managed with capecitabine-oxaliplatin plus bevacizumab, followed by maintenance therapy, achieving disease stabilization for at least 9 months. These cases illustrate the diagnostic and therapeutic complexities of STM, particularly with adenocarcinoma morphology that may mimic primary gastrointestinal neoplasms. Accurate diagnosis required exclusion of alternate primary sites and demonstration of chromosome 12 aberrations using FISH and next-generation sequencing. Our findings emphasize the importance of long-term follow-up in TGCT patients, particularly those with teratomatous elements, and highlight the value of cytogenetic and molecular profiling in confirming STM and identifying potential therapeutic targets. Given the rarity of STM, especially in metastatic or recurrent settings, there is an urgent need for standardized diagnostic protocols and evidence-based treatment strategies. These cases support the use of tumor-specific chemotherapy regimens guided by the histological and molecular characteristics of STM.

Cancer is a deadly disease affecting millions of people worldwide. Circulating tumor cells (CTCs) represent a critical link between primary malignancies and metastasis, acting as key players in cancer dissemination, progression, and recurrence. Although rare, CTCs offer a valuable, non-invasive window into tumor biology and the evolution of disease in patients. CTCs can exist as single cells in the circulation, but some are shed and travel in larger groups, referred to as CTC clusters. These clusters possess a greater oncogenic potential compared to individual CTCs. In this review, we aim to provide insight into the dynamic biological processes underlying CTC generation, biology, and survival, with a focus on epithelial-to-mesenchymal transition (EMT) and beyond like cancer stem cells (CSCs), cellular plasticity, and senescence. A crucial aspect of CTC biology is EMT, a process that imparts cancer cells with increased motility, invasiveness, resistance to apoptosis, and the ability to intravasate and evade the immune system. Beyond EMT the cancer cells show further plasticity, allowing epithelial tumor cells to adopt mesenchymal or hybrid phenotypes, which enables adaptation to a changing microenvironment and enhances therapy resistance. Moreover, a subset of cancer cells can acquire stem cell-like properties, including self-renewal and tumor-initiating capacity. EMT, along with processes such as dedifferentiation, contributes to the generation of cancer stem cells. In recent years, studies have also highlighted the complex and paradoxical role of senescence in CTC biology. While senescence typically results in permanent cell cycle arrest, in cancer cells it may be reversible and can promote tumor cell dormancy, immune evasion, and metastatic reactivation. By exploring the connections between CTCs, EMT, CSCs, plasticity, and senescence, we aim to shed light on the unique biology of CTCs, their metastatic potential, and their contributions to tumor heterogeneity. We hope that a better understanding of these processes will help advance the development of novel biomarkers and therapeutic targets for solid tumors beyond EMT.

Background: Follicular lymphoma (FL) is an indolent yet incurable B-cell lymphoma subtype commonly treated with a combination of bendamustine and anti-CD20 antibodies such as rituximab. While the standard administration involves a 2-day dosing schedule, the COVID-19 pandemic prompted the exploration of a 1-day regimen to reduce hospital visits for immunocompromised patients. This study aimed to compare the efficacy and safety of 1-day versus 2-day bendamustine regimens.

Methods: We conducted a retrospective analysis of 144 patients with FL, marginal zone lymphoma, mantle cell lymphoma, or Waldenström macroglobulinemia treated at the Department of Internal Medicine and Hematology, Semmelweis University between 2015 and 2023. All patients received bendamustine combined with either rituximab or obinutuzumab. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and toxicity. Kaplan-Meier survival analysis and appropriate statistical tests were applied.

Results: The median PFS for the cohort was 69.47 months; OS was not reached. Despite receiving a significantly lower cumulative dose, and being significantly older, patients on the 1-day regimen had similar PFS (not reached vs. 69.47 months; p = 0.885) and no significant difference in OS (p = 0.147) compared to the 2-day group. Adverse events were more frequent in the 2-day regimen group, including severe side effects, such as neutropenia (p = 0.044).

Conclusion: A 1-day bendamustine regimen may offer comparable efficacy to the standard 2-day schedule, with a potentially more favorable toxicity profile and better convenience, especially in older or more vulnerable patient populations. These findings warrant further investigation in prospective randomized trials to establish optimal dosing strategies.

Cancer metastasis, driven by cell migration, remains the leading cause of cancer-related deaths. In breast cancer, its high metastatic potential underscores the need for better preclinical models to bridge the gap between laboratory findings and clinical outcomes. However, studying migration in vitro remains challenging due to the complexity of tumour invasion and the difficulty of replicating physiologically relevant conditions. Traditional two-dimensional (2D) models, such as the scratch assay and transwell migration assay, offer simplicity and reproducibility but fail to capture the tumour microenvironment and dynamic migration behaviours. Advanced three-dimensional (3D) models, including spheroids, organoids, microfluidic systems, and organ-on-a-chip platforms, provide more physiologically relevant conditions but are often limited by cost and technical complexity. This mini-review provides an overview of widely used in vitro models for studying breast cancer migration and evaluates their respective advantages, limitations, and future potential. While no single system currently achieves the ideal balance between physiological relevance and practical accessibility, combining complementary tools remains the most effective strategy for investigating the metastatic cascade. Continued innovation in in vitro platforms is essential for improving translational accuracy and supporting the development of more effective anti-metastatic therapies.

Sarcomas are a heterogeneous group of rare and aggressive malignancies and have a propensity to metastasize to the thoracic cavity. While sarcoma lung metastasectomy is an established modality, only scarce information is available about potential prognostic factors for sarcoma patients with pleural dissemination. Accordingly, all consecutive sarcoma patients treated at our thoracic surgery department between 2010 and 2023 with pleural sarcomatosis and/or malignant pleural effusion were retrospectively analyzed. Preoperative circulating biomarker values were collected at the time of first pleural involvement. Overall survival was calculated from the first sarcoma diagnosis as well as from the first diagnosis of pleural dissemination. 98 patients (42 female) were included in the cohort with a median age of 54.6 years (range: 15.9-84.3 years) at the time of pleural involvement. 77 patients had soft tissue sarcoma, while 21 patients had primary sarcoma in the bone including 4 chondrosarcoma. Among the 19 different sarcoma types, synovial sarcoma (13%), liposarcoma (11%), undifferentiated pleomorphic sarcoma (11%), Ewing (like) sarcoma (10%) and leiomyosarcoma (9%) were the most frequent. Pleural dissemination was mostly metachronous, while only 7 cases were synchronous. The median pleural dissemination-free interval was 17.1 months after sarcoma diagnosis. The median overall survival after pleural dissemination was 12 months. WBC values outside the normal range had no significant impact on overall survival. High LDH (>250 U/L) and CRP (>1 mg/dL) conferred significantly lower overall survival (8.6 months vs. 19.1 months (p < 0.0001) and 4.9 months vs. 29 months (p < 0.0001), respectively). Albumin alone showed no prognostic impact, however, the modified Glasgow prognostic score (0, 1, and 2) was a strong prognosticator (20.4 vs. 8.6 vs. 1.7 months (p < 0.0001). In a multivariable analysis, CRP remained a significant prognostic factor. In conclusion, routine circulating biomarkers carry prognostic information for sarcoma patients with pleural dissemination and should be considered for risk stratification and personalized therapeutic decisions.