Impact of SPARC expression on outcome in patients with advanced pancreatic cancer not receiving nab-paclitaxel: a pooled analysis from prospective clinical and translational trials.
BACKGROUND
Conflicting results on the role of secreted protein acidic and rich in cysteins (SPARC) expression have been reported in resected pancreatic ductal adenocarcinoma (PDAC), and its prognostic and/or predictive role in advanced PDAC (aPDAC) has not been extensively investigated yet. This study was designed to evaluate SPARC expression as a biomarker in aPDAC patients (pts) not receiving nab-paclitaxel.


METHODS
Using immunohistochemistry, we examined the stromal as well as the tumoral (i.e., cytoplasmic) SPARC expression in tumour tissue (primary tumours and metastases) of 134 aPDAC pts participating in completed prospective clinical and biomarker trials. The SPARC expression levels were correlated to the pts' clinicopathological parameters and survival times.


RESULTS
Sixty-seven per cent of the analysed tumours showed high stromal SPARC expression, which was not associated with overall survival (OS, median 9.1 vs 7.6 months, P=0.316). A positive cytoplasmic SPARC expression was detected in 55% of the tumours and correlated significantly with inferior progression-free survival (PFS, 6.2 vs 8.6 months, P=0.004) and OS (7.8 vs 8.4 months, P=0.032). This association was strongest for pts, where primary tumour tissue was examined (PFS: 6.7 vs 10.8 months, P=0.004; OS: 7.9 vs 11.9 months, P=0.030), whereas no significant correlation was detected for pts, where only metastatic tissue was available (PFS: 5.8 vs 6.6 months, P=0.502; OS: 7.0 vs 7.8 months, P=0.452). In pts receiving gemcitabine-based chemotherapy cytoplasmic SPARC expression was significantly associated with an inferior PFS and OS (PFS: 6.2 vs 9.2 months, P=0.002; OS 7.3 vs 9.9 months, P=0.012), whereas no such association was detected for stromal SPARC expression or for pts receiving fluoropyrimidine-based chemotherapy.


CONCLUSIONS
We identified cytoplasmic SPARC expression in the primary tumour as a biomarker associated with inferior PFS and OS in aPDAC. Cytoplasmic SPARC expression may furthermore act as a negative predictive biomarker in pts treated with gemcitabine-based chemotherapy.
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany.
Steffen
S
Ormanns
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Michael
M
Haas
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany.|Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Sibylle
S
Baechmann
Department of Surgery, Jena University Hospital, Jena, Germany.
Annelore
A
Altendorf-Hofmann
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany.|Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Anna
A
Remold
Department of Internal Medicine II, Klinikum Chemnitz gGmbH, Chemnitz, Germany.
Detlef
D
Quietzsch
Department of Hematology and Oncology, Mutterhaus der Boromaeerinnen, Trier, Germany.
Michael R
MR
Clemens
Department of Internal Medicine III, Klinikum Karlsruhe, Karlsruhe, Germany.
Martin
M
Bentz
Department of Gastroenterology and Oncology, Klinikum Esslingen, Esslingen, Germany.
Michael
M
Geissler
Department of Hematology and Oncology, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany.
Helmut
H
Lambertz
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Stephan
S
Kruger
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany.
Thomas
T
Kirchner
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Volker
V
Heinemann
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Stefan
S
Boeck
D000465:Algorithms; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000378:metabolism*; D017239:Paclitaxel / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D015676:Osteonectin; D017239:Paclitaxel