SPARC expression in resected pancreatic cancer patients treated with Gemcitabine: results from the CONKO-001 study
Menée à partir d'échantillons tumoraux prélevés sur 160 patients atteints d'un cancer du pancréas traité par résection et inclus dans un essai de phase III évaluant la gemcitabine en traitement adjuvant, cette étude évalue la valeur pronostique de l'expression de SPARC
Background : Previous investigations in pancreatic cancer suggested a prognostic role for SPARC (secreted protein acidic and rich in cysteine) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared to untreated patients.
Patients and Methods : CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine as compared to observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue-microarrays to evaluate its impact on patient outcome.
Results : Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: p= 0.005, OS: p=0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: p=0.007, OS: p=0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: p=0.041, OS: p=0.011). Again the effect was restricted to patients treated with gemcitabine. In multivariable analysis, SPARC expression was independently predictive of patient outcome.
Conclusions : Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.Trial registration ISRCTN34802808.
Annals of Oncology , résumé, 2014