The expression of members of the GATA family of proteins and their prognostic value has been previously investigated in different tissues; however, there is limited data on the role of GATA6 and GATA3 in esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC). We aimed to assess the distinct expression and prognostic roles of GATA6 and GATA3 in 52 cases of esophageal carcinoma and to correlate these findings with clinicopathologic parameters and patient outcomes. GATA6 was expressed in 55% of ADC cases, 12.5% of SCC cases, and 15% of Barrett esophagus (BE) cases ( P =0.000). GATA6 was significantly associated with high tumor grade and stage ( P =0.015 and 0.011, respectively), perineural invasion ( P =0.004), tumor size ( P =0.004), and lymph node status ( P =0.037). GATA3 was expressed in 21.9% of SCC, while no expression was detected in ADC and BE ( P =0.027). GATA3 was significantly associated with low tumor grade and stage ( P =0.031 and 0.007, respectively). GATA6 was associated with poor overall survival (OS) ( P =0.000) and poor disease-free survival (DFS) ( P =0.000). No association was found between GATA3 expression and OS ( P =0.477) and DFS ( P =0.096). In conclusion, esophageal ADC was positive only for GATA6, whereas SCC was positive for both markers, with higher GATA3 expression. GATA6 may be a poor prognostic indicator for esophageal carcinoma.
The Hippo pathway has been implicated in the tumorigenesis of hepatocellular carcinoma (HCC). We aimed to determine the expression of Hippo pathway-related proteins in HCC using immunohistochemical staining and compare the data among patients with different underlying clinical background diseases. We collected 40 resected HCC formalin-fixed paraffin-embedded samples and categorized them into 4 groups according to pre-existing conditions [17 samples of alcohol consumption (HCC-A) and 6, 8, and 9 samples with hepatitis B virus infection (HCC-B), hepatitis C virus infection (HCC-C), and metabolic diseases (HCC-M), respectively]. Using immunohistochemistry, we investigated the Hippo pathway-related proteins YAP1, CADM1, and SOX9. Hypertension was the most common disease (72.5%) among patients with HCC, followed by diabetes mellitus (47.5%). Regarding the background liver disease, significant findings of steatohepatitis (SH) were observed in the HCC-A (35.3%) and HCC-M (88.9%) groups compared with those in the HCC-B (16.7%) and HCC-C (0%) groups. A significant finding of metabolic dysfunction-associated SH (MASH) was also observed in the HCC-M group (88.9%), and liver cirrhosis was predominantly observed in the HCC-C group (100%). Twenty-seven patients had Hippo-inactive status, and 13 patients had active status. SH was more predominant in the HCC-M group with Hippo inactivity (100%) than in the HCC-A group (50.0%). The average tumor size was significantly larger in the Hippo-inactive group than in the Hippo-active group. Hippo pathway-associated proteins could serve as potential therapeutic targets for MASH and MASH-related HCC if the Hippo pathway is inactivated.
Gastrointestinal stromal tumors (GISTs) with PDGFRA mutations represent a distinct subset with characteristic clinicopathological features and important therapeutic implications. The diagnostic performance of PDGFRA immunohistochemistry (IHC) as a phenotypic correlate of PDGFRA mutation status requires further evaluation. This study aimed to assess the diagnostic performance and reproducibility of PDGFRA IHC against PDGFRA mutation status as the reference standard. A total of 117 tumors were analyzed (19 PDGFRA -mutant, 40 non- PDGFRA , 49 GISTs of undetermined genotype, 9 non-GIST mimics). IHC for KIT, DOG1, CD34, and PDGFRA was performed on full sections and tissue microarrays, and 3 pathologists independently scored intensity, extent, and Golgi-pattern accentuation. PDGFRA -mutant GISTs were predominantly gastric with epithelioid or mixed morphology. Sixteen carried D842V, whereas 3 had exon 18 deletion or exon 12 mutations. KIT expression was reduced (47.4%) compared with non- PDGFRA -mutant GISTs (85%), while DOG1 remained consistently positive. Overall, PDGFRA expression was observed in 94.7% of PDGFRA -mutants compared with 32.5% of non- PDGFRA -mutants ( P< 0.001), and Golgi-pattern accentuation was present in 89.5% (17/19) of PDGFRA -mutants versus 7.5% (3/40) of molecularly confirmed non- PDGFRA -mutants ( P <0.001). Among non-GIST mimics, only a monophasic synovial sarcoma showed diffuse PDGFRA positivity. Interobserver agreement for PDGFRA was substantial (κ=0.691). PDGFRA IHC showed 95% sensitivity and 78% specificity but did not distinguish D842V from non-D842V variants. PDGFRA IHC correlates with PDGFRA -mutant genotype when diffuse Golgi-type staining is observed in a gastric epithelioid or mixed tumor showing reduced KIT expression. However, therapeutic selection—particularly for avapritinib—requires precise detection of D842V variants, which mandates molecular sequencing.
Leucine-rich repeat-containing 15 (LRRC15) is a membrane protein whose overexpression has been linked to poorer survival outcomes in various malignant neoplasms. However, its role in distal extrahepatic bile duct carcinoma (DBDC) remains unclear. LRRC15 protein expression in tumor cells and stroma was evaluated with 196 surgically resected DBDCs, and compared with clinicopathological variables, including patients' overall survival (OS) and recurrence-free survival (RFS). LRRC15 protein expression was identified in stroma of 21 DBDCs (11%) and tumor cells in 67 cases (34%). On the basis of the combined expression patterns of LRRC15, DBDCs were classified into 4 groups: LRRC15 cancer+/stroma- (25%), cancer-/stroma+ (2%), cancer+/stroma+ (9%), and cancer-/stroma- (64%). The stromal LRRC15+ group exhibited more frequent pancreatic invasion compared with the stromal LRRC15- group ( P =0.004*). The LRRC15 cancer+/stroma+ group showed the most frequent pancreas invasion ( P =0.016*). The patients with stromal LRRC15+ group had significantly worse OS (5-year survival rate, 15.4% vs. 31.6%; P =0.013*) and RFS (19.1% vs. 38.9%; P =0.005*) compared with those in the stromal LRRC15- DBDCs. Stromal LRRC15 expression was significantly associated with poor prognosis and showed a strong trend toward being an independent prognostic factor for both OS ( P =0.051) and RFS ( P =0.061). Patients with DBDCs in the LRRC15 cancer+/stroma+ group had the worst RFS ( P =0.010*) and OS ( P =0.008*) by univariate analysis. LRRC15 overexpression was observed in a subset of DBDCs and was associated with pancreatic invasion and worse OS and RFS. Consequently, LRRC15 expression can be used as an indicator of poor survival in patients with DBDCs, particularly when both cancer cells and stromal expression are present.
Formalin has long served as the standard fixative in histopathology; however, its limitations-such as antigen masking, nucleic acid degradation, and carcinogenicity-have prompted the search for safer alternatives. APAFIX, a formalin-free fixative, was developed to maintain diagnostic integrity while improving safety in routine tissue handling. This pilot study was conducted to compare the efficiency of the APAFIX solution with formalin in preserving human histologic tissue architecture and cellular morphology as assessed by routine Hematoxylin and Eosin (H and E) staining. Ten human biopsies from different tissue origins underwent standard H and E staining using the routine paraffin technique after 6 to 8 hours of postfixation in either APAFIX or 10% formalin. A blinded pathology review evaluated key histologic parameters, nuclear detail, lymphocyte visualization, fibrous tissue integrity, and overall tissue architecture, using a 10-point scoring system. Results revealed that APAFIX fixing solution was as effective as formalin fixation in terms of tissue quality during processing and sectioning, and in preserving architectural and cellular morphology. APAFIX solution showed enhanced nuclear detail and lymphocyte visualization with occasional fixation artifacts, such as pseudolipomatosis, observed in epithelial tissue. Formalin was more effective in preserving fibrous and epithelial areas. Overall, APAFIX demonstrated sufficient diagnostic performance across the studied pathologic biopsies. APAFIX is a promising formalin-free alternative for histologic tissue fixation, offering enhanced preservation of critical cellular features and eliminating health hazards associated with formalin. Further large-scale studies are warranted to validate its application across broader diagnostic settings and specialized staining techniques.
