Intrahepatic cholangiocarcinoma and gallbladder cancer: Distinguishing molecular profiles to guide potential therapy

Mary Potkonjak, John T. Miura, Kiran K. Turaga, Fabian M. Johnston, Susan Tsai, Kathleen K. Christians, T. Clark Gamblin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1119-1123
Number of pages5
JournalHPB
Volume17
Issue number12
DOIs
StatePublished - Dec 2015

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Potkonjak, M., Miura, J. T., Turaga, K. K., Johnston, F. M., Tsai, S., Christians, K. K., & Gamblin, T. C. (2015). Intrahepatic cholangiocarcinoma and gallbladder cancer: Distinguishing molecular profiles to guide potential therapy. HPB, 17(12), 1119-1123. https://doi.org/10.1111/hpb.12504