Bladder carcinomas in patients with neurogenic bladder and urinary schistosomiasis: are they the same tumors?

PURPOSE: The aim of our study was to evaluate and compare the expression of different immunohistochemical markers in Bladder Carcinomas (BC) in patients with Neurogenic Bladder (NB) and Urinary Schistosomiasis (US) infection. MATERIALS AND METHODS: We collected tissue samples from patients with Neurogenic Bladder and Bladder Carcinoma (NBC Group) and from patients with Urinary Schistosomiasis infection and Bladder Carcinoma (SBC Group). We compared to these two groups to control samples from resection from patients with Urinary Schistosomiasis without Bladder Carcinoma (US Group); we also investigate patients' characteristics according to urothelial transitional cell carcinoma (TCC), and squamous cell carcinoma (SCC) histopathological differentiation. The expression of markers in all groups (CK7, CK14, CK20, FoxP3, GATA3, STAG2, CD3, CD8, Ki67, and P53) was analyzed using immunohistochemistry of tissue micro-array sections (TMA). RESULTS: Overall, 136 patients were included in the study (n = 72 in the NBC group, n = 33 in the SBC group, and n = 31 in the US group). In the TCC subgroup, the expression of CK7, CK14, CK20, and Ki67 was significantly higher compared to US controls (p 0.002; p < 0.001; p 0.036; p < 0.001). In the SCC subgroup, the expression of CK7, CK14, and CK20 was significantly higher compared to US controls (p 0.007; p < 0.001; p 0.005). Both in TCC and SCC subgroups, no difference in the expression of any tested markers was found comparing NBC and SBC groups. In US group, a significant higher expression of STAG2 was found compared to SCC subgroup (p 0.005). CONCLUSION: Based on our results, the profile of immunohistochemical biomarkers' expression in both NBC and SBC groups is similar.

A study of the immunohistochemical profile of bladder cancer in neuro-urological patients by the French Association of Urology.

PURPOSE: To establish whether the expression of markers of cell differentiation (CK7, CK14, CK20, GATA3), apoptosis (p53), proliferation (Ki67, STAG2) and peri-tumoural lymphocytes (CD3, CD8), provides specific information about urothelial carcinogenesis in neuro-urological patients with bladder cancer (NBC). METHODS: Tissue samples from NBC were retrieved from 15 centres in France and compared to control samples from non neuro-urological patients with bladder cancer (NNBC) and from neuro-urological patients without bladder cancer (NB). The expression of CK7, CK14, CK20, GATA3, p53, Ki67, STAG2, CD3 and CD8 markers was analysed using immunohistochemistry of tissue microarray sections. RESULTS: Overall, tissue samples from 124 patients were included in the study (n = 72 NBC, n = 26 NNBC and n = 26 NB). Muscle invasive bladder cancer (MIBC) was found in 52 NBC patients (72.2%) and squamous cell differentiation in 9 (12.5%). In NBC samples, the expression of CK20 and GATA3 was significantly more frequent in NMIBC compared to MIBC (p = 0.015 and p = 0.004, respectively). CK20 and GATA3 were significantly more expressed in NBC compared to NNBC (p < 0.001 and p = 0.010, respectively). The expression of CK14, Ki67, CD3 and CD8 was significantly more frequent in NBC than in NNBC samples (p = 0.005, p < 0.001, p < 0.001 and p < 0.001, respectively). The expression of CD3 and CD8 was similar in NBC and NB samples. CONCLUSION: In NBC, markers of basal differentiation, proliferation and peri-tumoural lymphocytes were significantly more expressed compared to NNBC controls. These results suggest the aggressiveness of NBC and the role of chronic inflammation in the carcinogenesis of bladder cancer in neuro-urological patients.

The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. METHODS: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. RESULTS: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). CONCLUSION: This study's results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II.

Therapeutic strategies to overcome EGFR mutations as acquired resistance mechanism in ALK-rearranged non-small-cell lung cancer: Case Reports.

Introduction: ALK tyrosine kinase inhibitors (ALK TKIs) have improved prognosis in ALK-rearranged (ALK +) non-small-cell lung cancer (NSCLC). However, drug resistance mechanisms occur inevitably during the course of treatment leading to disease progression. Activation of epidermal growth factor receptor (EGFR) bypass signaling pathway is an uncommon cause of acquired resistance to ALK TKIs. Method: We present two patients with EML4-ALK rearranged NSCLC, developing an acquired EGFR resistance mutation after receiving multiple lines of ALK TKIs. Results: While preclinical models have showed encouraging data, there is a critical need for clinical studies on treatment strategies to overcome this drug resistance. Three real-life therapeutic approaches were used in this report: i) using brigatinib, an inhibitor targeting both ALK and EGFR tyrosine kinases; ii) combining two ALK TKIs together; and iii) delivering doublet platinum chemotherapy. In case 1, time to treatment failure (TTF) was 9.5 months with brigatinib; in case 2, TTF was 10 months with combined TKIs (osimertinib and brigatinib), whereas TTF with chemotherapy was only 2 months. Tolerability profile TKIs combotherapy was acceptable. Conclusion: These case reports underline the therapeutic complexity of EGFR-acquired resistance mutation in ALK+ NSCLC and offers some leads to solve this real-life clinical challenge.

Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas.

BACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. CONCLUSION: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.