👤 Julia M Sołek

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Accurate differentiation between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is critical for informing personalized therapies. Thyroid transcription factor-1 (TTF-1) and p40 are traditionally regarded as mutually exclusive markers of ADC and SCC, respectively. However, a subset of tumors exhibits co-expression of TTF-1 and p40, presenting diagnostic challenges and suggesting underlying biological distinctiveness. This study aimed to characterize the clinicopathological, molecular, and immunohistochemical features of NSCLCs co-expressing TTF-1 and p40, in order to clarify their biological and clinical significance. A retrospective analysis was performed on NSCLC cases diagnosed at the Central Clinical Hospital of the Medical University of Łódź between May 2021 and November 2022. Clinicopathological and survival data were collected. Tumors co-expressing TTF-1 and p40 underwent immunohistochemical evaluation and RNA/DNA-based next-generation sequencing (NGS). Of 94 NSCLC cases analyzed, 18 (19.1%) demonstrated co-expression of TTF-1 and p40. These tumors were significantly more likely to exhibit solid growth patterns compared to control cases (P=0.03), but no significant difference in overall survival (OS) was observed (P=0.46). Among 17 samples subjected to NGS, genetic alterations were identified in 15 (88.2%) cases, with NSCLCs co-expressing TTF-1 and p40 appear to represent a biologically distinct and poorly differentiated subgroup, frequently associated with Show less

The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear. Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level. FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes. FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance. Show less

Fibroblast growth factor receptor 2 (FGFR2) activation is associated with endocrine therapy resistance in luminal breast cancer (BC) An Two clusters of ER+ IDC tumours were identified based on the stromal gene expression profile. While both clusters had similar tumour stages and hormone receptor statuses, multivariable analysis adjusted for clinical factors revealed a significant association between Stromal profiles modulate the prognostic significance of Show less