Effect of neoadjuvant treatment with gemcitabine with nab-paclitaxel on SPARC and Ki-67 in patients with resectable pancreatic adenocarcinoma.

Abstract

322 Background: Nab-paclitaxel (nab-P) and gemcitabine (Gem) improve survival in metastatic pancreatic cancer (PCa). We sought to determine the impact of nab-P and Gem on the primary tumor and associated microenvironment in neoadjuvant treatment (NAT). Methods: All patients in the GAIN-1 study (NCT01470417) received NAT with nab-P and Gem with or without radiation depending on risk status. A comparator group without NAT was matched for age, sex, race, resection status, smoking, primary tumor site, and tumor size. Surgical specimens of tumor, associated stroma and lymph nodes were analyzed. Routine immunohistochemistry (IHC) for Ki-67 and TUNEL was performed. Immunolabeling was assessed using anti-SPARC antibody (Invitrogen) with scoring consistent with prior reports: Negative = intensity absent to weak (+) with extent <10%; Positive = intensity moderate (++) to strong (+++) with extent ≥ 10%. For Ki-67 and TUNEL, the percentage of positive tumor cells was averaged over four HPF/specimen. Study was conducted with IRB approval. Results: A total of 30 unique patients were included in this analysis, 8 NAT cases and 22 matched controls. Clinical outcomes have been previously reported. Minimal to no SPARC expression was noted in either group of tumor cells. However, stromal SPARC expression was markedly reduced in NAT group (mean 2.88 ± 0.69%) compared to controls (28.43 ± 5.80%; p = 0.0002). Ki-67 was reduced in NAT group compared to controls (10.5 ± 2.83% vs. 36.76 ± 4.32%; p = 0.0004). TUNEL stain revealed a trend toward lower levels in NAT group (mean 1.13 ± 0.30% vs. 1.62 ± 0.31%; p = 0.574). SPARC, Ki-67 and TUNEL did not correlate with survival. Conclusions: SPARC expression in pCa primary tumors is low. Neoadjuvant nab-P and Gem significantly decreased stromal SPARC and tumor Ki-67. There was no change in TUNEL expression, indicating a population of residual viable cells. Additional stromal microenvironment change analysis in response to treatment is ongoing.