Polish Journal of Pathology最新文献

Our previous study demonstrated that HMGB1 may suppress M1 macrophage polarisation and mitigate the progression of calcific aortic valve disease (CAVD). However, the role of HMGB1 in regulating macrophage-mediated valvular calcifi-cation remains to be further explored. Serum samples from healthy individuals and CAVD patients with varying severity were collected and analysed by ELISA. Immunofluorescence staining of human heart tissue arrays assessed macrophage infiltration in calcified valves. A macro-phage-aortic valve interstitial cell (haVIC) co-culture system was used to examine the effects of reHMGB1-treated macrophages. RUNX2 and osteopontin mRNA expression were measured by RT-qPCR, and alkaline phosphatase (ALP) staining was performed to evaluate calcification. HMGB1 levels were significantly reduced in severe CAVD patients than controls. Immunofluorescence staining revealed increased CD68 expression in calcified valve samples, indicating macrophage infiltration. In the macrophage-haVIC co-culture system, macrophages pretreated with reHMGB1 led to reduced RUNX2 mRNA expression and lower ALP activity in haVICs, suggesting a potential inhibitory effect of HMGB1 on valvular calcification. HMGB1 may have the potential to suppress inflammation and mitigate aortic valve calcification, making it a promising therapeutic target for preventing the progression of aortic stenosis.

This study aimed to investigate the expression profile of FOXC1 in molecular sub-types of invasive breast cancer. Additionally, it sought to explore the association between FOXC1 expression and clinicopathological prognostic parameters to eval-uate its potential diagnostic and therapeutic implications. A total of 122 invasive breast carcinoma cases from excision specimens were an-alysed. Immunohistochemical staining for FOXC1 was performed, with nuclear expression > 1% considered positive. The correlation between FOXC1 expression, molecular subtypes, and prognostic parameters was examined. A significant negative correlation was found between FOXC1 expression and ER, PR, and HER2 in 122 cases, while FOXC1 expression was notably higher in the triple-negative breast cancer (TNBC) subtype. Additionally, FOXC1 expression showed a significant positive correlation with nuclear grade, histological grade, Ki67 index, and prognostic stage. FOXC1 expression was found to be higher in TNBCs compared to other molecular subtypes, and FOXC1 expression was negatively correlated with hormone recep-tors and HER2. On the other hand, FOXC1 was significantly associated with high proliferation index, high-grade tumour, and prognostic stage. These findings sug-gest that high FOXC1 expression may indicate aggressive behaviour and may be a predictive marker for poor prognosis.

Deep learning (DL) has transformed medical imaging, particularly in the realm of oral cancer (OC) diagnosis using histopathological images. Timely detection of OC is es-sential for enhancing precision medicine and saving lives. However, incorrect diagnosis may impede effective treatment. In this study, we have proposed a DL model for OC classification, enhanced diagnosis decision-making and interpretability. We achieve this by starting with colour normalisation of histopathology images using the Vaha-dane 3-stain parameter normalisation and watershed segmentation method, followed by tiling and augmentation. Key features are selected using the weighted Fisher score (WFS) to address class imbalance. The U-Net classifier has been improved by using feature-based inputs instead of full images, reducing computational complexity and training time. The integration of Vahadane normalisation for consistent preprocessing across samples, WFS, and explainable artificial intelligence (XAI) addresses critical challenges in histopathological image analysis. The proposed model surpasses exist-ing approaches with a classification accuracy of 99.54%, and it outperforms Dense- Net201 and VGG10 in precision and reliability. The efficiency in handling imbal-anced datasets and explainability features make it suitable for early precise OC detec-tion, which can reduce diagnostic errors and enhance treatment outcomes.

TROP-2 is a transmembrane calcium signaling molecule that is detected at a high rate (63%) in breast cancers. There are conflicting data on its relationship with subtypes, clinical, and pathological data in breast cancer. TROP-2 expression levels were evaluated by immunohistochemistry, and the H-score method was used to analyze the data. This evaluation was conducted on a total of 79 patients diagnosed with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) positive (HER2-E) breast cancer. The study also investigated the relationship between TROP-2 expression levels and the clinical-pathological features observed in patients diagnosed with TNBC and HER2-E. A total of 62 TNBC (78.5%) and 17 HER2-E (21.5%) cases were analyzed in the study. The presence of high TROP-2 (H-score > 100) was detected in 87% of the TNBC group and 94% of the HER2-E group. Among the pathological parameters, only low H-score values were found to have a statistically significant correlation with mucinous morphology; however, no significant correlation was found with other pathological parameters, including CerbB2 expression status. No significant relationship was found between H-score and clinical parameters. Furthermore, TROP-2 expression in HER2-E cancers is notably elevated. Further studies with larger series are required to clarify expression rates in mucinous tumors.

The education curriculum of the faculty of dentistry includes both general pathol-ogy and oral pathology courses. In our planned study, we aimed to determine the needs of dentists who graduated from the faculty of dentistry and received special-isation training for pathology information in their active professional lives and the importance of pathology education according to their fields of specialisation. Survey questions: Applications were made to 115 dentists who graduated from the faculty of dentistry, received specialist training, and worked in the clinic. While the benefit of pathology training in the dentist's professional life was oral and maxillofacial surgery, it was followed by periodontology, radiology, and oral diagnosis specialties. They also stated that they sent samples and evaluated reports in the fields of oral and maxillofacial surgery, periodontology, radiology, and oral diagnosis. In our study, the areas where specialist physicians benefit from pathology training in the clinic are those where the subjects overlap more with the sections in the training curriculum. It is necessary to provide adequate training in basic medical sciences to train dentists as physicians who do not perceive the patient only in terms of mouth and teeth, but can evaluate the patient as a whole and provide the right guidance at the right time. Integration should be ensured between basic sciences, dentistry, and clinical sciences. For pathology education to be permanent and useful, a curriculum should be designed with innovative teaching methods that are department-specific and practice-based, appropriate to the needs of the clinic. Dentistry graduates can improve patient outcomes and enhance their personal de-velopment by deepening their understanding of pathology education.

Programmed death-ligand 1 (PD-L1) guides immune checkpoint inhibitor use in non-small cell lung cancer (NSCLC), yet its variation by age and histology remains uncertain. We retrospectively evaluated 1,606 consecutive NSCLC cases (2017-2022) with PD-L1 immunohistochemistry (IHC) on formalin-fixed, paraffin- embedded samples. Patients were grouped by age (< 60, 60-79, ≥ 80 years) and tumor proportion score (TPS), categorized as < 1%, 1-49%, or ≥ 50%. Associations were tested using the ² test, and independent predictors were identified using multinomial logistic regression. High PD-L1 expression (TPS ≥ 50%) occurred in 33.6% of patients, intermediate (1-49%) in 23.6%, and negative (< 1%) in 42.7%. Programmed death-ligand 1 expression ≥ 1% was most frequent in squamous cell carcinoma (63.0%), followed by adenocarcinoma (55.0%), and was least common in large cell carcinoma (36.0%; p = 0.002). Overall proportions of PD-L1 ≥ 1% did not differ significantly by age. However, patients aged ≥ 80 had nearly twice the likelihood of high expression compared to those < 60 (relative risk ratio, 1.92; 95% CI: 1.11-3.34; p = 0.02), independent of the histotype. Programmed death-ligand 1 expression in NSCLC shows distinct histotype-related patterns and a modest, age-related trend toward higher values in the oldest group. These data support routine PD-L1 assessment and suggest that advanced age alone should not preclude consideration of immunotherapy. Findings may inform trial design and real-world treatment decision-making.

The purpose of this study is to explore the clinical and pathological characteristics as well as the molecular pathogenesis of patients with non-small cell lung cancer (NSCLC) transforming into small cell lung cancer (SCLC). We investigated 14 patients with advanced NSCLC that transformed into SCLC. Whole genome sequencing (WES) was applied to analyse 14 tumour specimens (including NSCLC and SCLC specimens from each patient) from 7 patients to detect genetic predictive factors for small-cell transformation. The clinicopatho-logical characteristics of these 14 patients were collected and analysed. In addition, a detailed literature review was conducted to identify similar cases of transforma-tion from NSCLC to SCLC. Fourteen cases were included. The basic condition of patients who had undergone the transformation was found to be similar to those individuals without any trans-formation. After SCLC transformation, the mutation spectrum changed: C>T de-creased and C>A increased. In comparison to the initial NSCLC, the copy number variants (CNV) burden in the transformed SCLC increased considerably in a subset of patients. Clonal evolution analysis revealed intriguing connections and notable differences between the genetic clones of the initial NSCLC and the transformed SCLC. It was found that the process of transformation took a longer time in fe-males compared to males. Furthermore, it was observed that the transformation time for LADC was longer compared to squamous cell carcinoma (SCC). Addition-ally, the analysis revealed that after completion of the transformation, the OS time for males was found to be longer than that for females. Secondary biopsy is a crucial step in assessing the genetic and histological alter-ations that occur after a patient develops resistance to their initial treatment. This procedure is vital not only for individuals who have been treated with tyrosine kinase inhibitors but also for those who have undergone chemotherapy or immuno-therapy. One interesting finding is that the mutation rate of p53 and RB1 in trans-formed SCLC is lower compared to de novo SCLC. Specifically, there is a decrease in the C > T mutation and an increase in the C > A mutation following transforma-tion. Moreover, the transformed SCLC appears to originate from the major clones of the initial NSCLC.

Leishmaniasis is a zoonosis caused by protozoans transmitted by sandflies. Immu-nosuppression is a risk factor for developing leishmaniasis in patients treated with TNF inhibitors for autoimmune diseases. A 65-year-old man with a 14-year histo-ry of psoriatic arthritis in treatment with methotrexate, treated with golimumab during the last 2.5 years, presented ulcerations of the buttocks and upper back. Histopathological findings allowed us to yield the diagnosis of cutaneous leishman-iasis. Therapy was suspended and the patient underwent appropriate treatment. Five cases of leishmaniasis in patients treated with golimumab were reported in literature and ten cases were mentioned in retrospective reviews.

Medullary thyroid carcinomas (MTCs) are 75% sporadic and 25% hereditary. This study aimed to determine the histopathological parameters and molecular changes of sporadic MTCs in a university hospital by targeted next-generation sequencing (NGS) including 62 genes. All RET mutations were missense mutations. EIF1AX was suggested by artificial intelligence as a gene of interest for further analysis; subsequent testing revealed a pathogenic missense mutation in this gene in a patient with advanced-stage disease, who died at the 25th month of follow-up due to liver metastasis. We identified different gene mutations that could be associated with nodal metastasis in the presence or absence of RET mutation. We identified mutations that may be involved in tumour progression and have prognostic significance, such as HRAS, MAP3K1, and EIF1AX. We observed KDR mutation in this cohort. Although driver mutations in sporadic medullary thyroid carcinoma (sMTC) mostly come from targeted NGS data in tumours from patients with localised disease, NGS findings can also be used for therapeutic purposes in advanced-stage sMTC cases with progressive local-regional or distant metastatic disease. We believe that additional studies should be conducted with a larger number of patients so that the findings can be included in the treatment guidelines to be prepared.