Faculty Collaboration Database

Intrahepatic cholangiocarcinoma and gallbladder cancer: distinguishing molecular profiles to guide potential therapy. HPB (Oxford) 2015 Dec;17(12):1119-23

Date

09/17/2015

Pubmed ID

26374242

Pubmed Central ID

PMC4644364

DOI

10.1111/hpb.12504

Scopus ID

2-s2.0-84947030321 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: Chemotherapy regimens for intrahepatic cholangiocarcinoma (ICC) and gallbladder adenocarcinoma (GC) remain interchangeable; however, response rates are frequently suboptimal. Biomarkers from ICC and GC patients were interrogated to identify actionable differences with potential therapeutic implications.

METHODS: From 2009 to 2012, pathological specimens from 217 ICC and 28 GC patients referred to Caris Life Sciences were evaluated. Specific testing by immunohistochemical analysis for 17 different biomarkers was performed.

RESULTS: In the collective cohort (n = 245), actionable targets included: 95% low thymidylate synthase (TS), 82% low ribonucleotide reductase subunit M (RMM) 1 and 74% low excision repair cross complementation group (ERCC) 1, indicating potential susceptibility to fluoropyrimidines/capecitabine, gemcitabine and platinum agents, respectively. Additional targets included TOPO1 (53.3% high, Irinotecan), MGMT (50.3% low, temozolomide), TOP2A (33% high, anthracyclines) and PGP (30.1% low, taxanes). Subgroup analysis by tumour origin demonstrated a differential biomarker expression pattern with a higher frequency of ICC tumours showing low levels of TS (99% versus 72%, P < 0.01), and RRM1 (85% versus 64%, P = 0.02) when compared with GC. Conversely a greater frequency of GC demonstrated high levels of TOPO1 (76% versus 50%, P = 0.02) versus ICC, indicating a potential increased benefit from irinotecan.

DISCUSSION: Differences in the molecular profiles between ICC and GC provide evidence that the two are distinct diseases, requiring different treatment strategies to optimize a response.

Author List

Potkonjak M, Miura JT, Turaga KK, Johnston FM, Tsai S, Christians KK, Gamblin TC

Authors

Kathleen K. Christians MD Professor in the Surgery department at Medical College of Wisconsin
Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin
Mary McLachlan MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Antineoplastic Combined Chemotherapy Protocols
Bile Duct Neoplasms
Biomarkers, Tumor
Cholangiocarcinoma
Diagnosis, Differential
Female
Gallbladder Neoplasms
Humans
Immunohistochemistry
Male
Middle Aged
Molecular Diagnostic Techniques
Molecular Targeted Therapy
Patient Selection
Predictive Value of Tests
Retrospective Studies