Predictive value of heparanase expression in the palliative therapy of pancreatic cancer.
OBJECTIVE
Patients with pancreatic ductal adenocarcinoma (PDA) have a median survival of less than six months from diagnosis. Palliative chemotherapy with the current standard gemcitabine does only marginally improve median survival. There may be subgroups of patients receiving palliative therapy that have a better prognosis. Factors predicting response to palliative therapy are ill-defined, though. Heparanase, an endoglycosidase degrading components of the extracellular matrix, promotes cell invasion, is involved in angiogenesis and plays a role in tumor metastases. It is expressed in PDA and its expression is associated with shorter postoperative survival after pancreatic resections.


METHODS
58 patients with inoperable PDA were treated with gemcitabine therapy. Tissue sections from primary or metastatic tumor were used for immunohistochemical analysis. Heparanase expression was determined and correlated to tumor response, time to progression and survival.


RESULTS
Heparanase expression was detectable by immunohistochemistry in 36 out of 58 (62%) patients analyzed. Overall survival was 7.4 vs. 13.3 months (p = 0.006) in heparanase-positive and -negative tumors, respectively. Progression-free survival was 1.3 vs. 3.4 months, respectively (p = 0.47).


CONCLUSIONS
Heparanase expression may be a useful marker to predict response to palliative therapy with gemcitabine in PDA.
Schoppmeyer
K
K
Department of Medicine II, Leipzig University, Germany.
Kronberg
J
J
Tannapfel
A
A
Mossner
J
J
Wittekind
C
C
Caca
K
K
D000230:Adenocarcinoma / Q000628:therapy*; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D005966:Glucuronidase / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D000093542:Gemcitabine; D000099175:Heparanase
D015415:Biomarkers; D003841:Deoxycytidine; D005966:Glucuronidase; D000093542:Gemcitabine; D000099175:Heparanase