European journal of cancer (Oxford, England : 1990) · 2026
Direct Tumor-Adipocyte Contact as a Prognostic Biomarker in Resected Pancreatic Ductal Adenocarcinoma.
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Günther Michael, Bräutigam Konstantin, Wartenberg Martin, Arslan Muhammed D, Sucher Robert, El-Mahrouk Mohamed, Neumann Jens, Grochowski Przemyslaw, Wenning Anna S, Gloor Beat, Dornieden Berna, Grützmann Robert, Pilarsky Christian, Hartmann Arndt, Eckstein Markus, Märkl Bruno, Matek Christian, Skok Kristijan, Ormanns Steffen, Reitsam Nic G
Аннотация
BACKGROUND: Direct tumor-adipocyte contact (TAC), also referred to as Stroma AReactive Invasion Front Areas (SARIFA), is an emerging histomorphologic biomarker, defined by histologically visible direct tumor-adipocyte interaction. Its prognostic relevance in pancreatic ductal adenocarcinoma (PDAC) has not been investigated across independent cohorts.
METHODS: In this international, real-world, multicenter study, TAC/SARIFA was assessed on 941 resected PDAC cases across five cohorts (Munich n = 400, Bern n = 215, Graz n = 111, Erlangen n = 101, TCGA n = 114). Clinicopathological correlations, survival analyses, and differential gene expression analyses were performed.
RESULTS: TAC/SARIFA positivity was present in 53% of evaluable cases and showed substantial interobserver agreement across seven pathologists (mean Cohen's kappa: 0.71). TAC/SARIFA-positive tumors were associated with higher nodal (pN) stage, higher tumor grade, and older patient age (each p < 0.01). TAC/SARIFA positivity was significantly associated with reduced overall survival (pooled median OS: 14.1 vs. 28.0 months, p < 0.001) and remained an independent prognostic factor in multivariate analysis (pooled HR 1.84, 95% CI 1.59-2.14, p < 0.001). A significant interaction between TAC/SARIFA and sex was identified (p < 0.001), with a stronger prognostic effect in males (HR 2.46) than in females (HR 1.50). Adjuvant chemotherapy was associated with longer OS in both TAC/SARIFA subgroups, with a greater absolute survival difference in TAC/SARIFA-positive patients. Bulk transcriptomic profiling revealed upregulation of leptin (LEP) and the basal-like marker KRT14 in TAC/SARIFA-positive tumors.
CONCLUSIONS: TAC/SARIFA is a robust, independent prognostic histomorphologic biomarker in PDAC with a sex-dependent effect. Its reproducible and quick assessment on routine H&E slides supports further investigation of its applicability for PDAC risk stratification.
METHODS: In this international, real-world, multicenter study, TAC/SARIFA was assessed on 941 resected PDAC cases across five cohorts (Munich n = 400, Bern n = 215, Graz n = 111, Erlangen n = 101, TCGA n = 114). Clinicopathological correlations, survival analyses, and differential gene expression analyses were performed.
RESULTS: TAC/SARIFA positivity was present in 53% of evaluable cases and showed substantial interobserver agreement across seven pathologists (mean Cohen's kappa: 0.71). TAC/SARIFA-positive tumors were associated with higher nodal (pN) stage, higher tumor grade, and older patient age (each p < 0.01). TAC/SARIFA positivity was significantly associated with reduced overall survival (pooled median OS: 14.1 vs. 28.0 months, p < 0.001) and remained an independent prognostic factor in multivariate analysis (pooled HR 1.84, 95% CI 1.59-2.14, p < 0.001). A significant interaction between TAC/SARIFA and sex was identified (p < 0.001), with a stronger prognostic effect in males (HR 2.46) than in females (HR 1.50). Adjuvant chemotherapy was associated with longer OS in both TAC/SARIFA subgroups, with a greater absolute survival difference in TAC/SARIFA-positive patients. Bulk transcriptomic profiling revealed upregulation of leptin (LEP) and the basal-like marker KRT14 in TAC/SARIFA-positive tumors.
CONCLUSIONS: TAC/SARIFA is a robust, independent prognostic histomorphologic biomarker in PDAC with a sex-dependent effect. Its reproducible and quick assessment on routine H&E slides supports further investigation of its applicability for PDAC risk stratification.