Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

Abstract

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Keywords: Anti-apoptotic protein; Chemotherapy; Endoscopic ultrasound-guided fine-needle aspiration; Liver tumor biopsy; Predictive marker.

Fig. 1

Representative immunohistochemical staining of Mcl-1 in specimens obtained using percutaneous ultrasound-guided liver tumor biopsy. Micrographs of pancreatic ductal carcinoma obtained using percutaneous ultrasound-guided liver tumor biopsy. (A) and (B): Well-differentiated adenocarcinoma (A: hematoxylin and eosin staining [HE], × 200) with more than 20% of the tumor cells in the cytoplasm showing immunoreactivity for Mcl-1 (B: immunohistochemical staining [IHC], × 200), which was considered positive. (C) and (D): Poorly differentiated adenocarcinoma (C; HE, × 200) with no cells showing immunoreactivity for Mcl-1 (D; IHC, × 200), which was considered a negative result.

Fig. 2

Comparison of progression-free survival (PFS) and overall survival (OS).