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.
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.
Authors: Rebecca M Dodson; Matthew J Weiss; David Cosgrove; Joseph M Herman; Ihab Kamel; Robert Anders; Jean-Francois H Geschwind; Timothy M Pawlik Journal: J Am Coll Surg Date: 2013-07-24 Impact factor: 6.113
Authors: Juan Valle; Harpreet Wasan; Daniel H Palmer; David Cunningham; Alan Anthoney; Anthony Maraveyas; Srinivasan Madhusudan; Tim Iveson; Sharon Hughes; Stephen P Pereira; Michael Roughton; John Bridgewater Journal: N Engl J Med Date: 2010-04-08 Impact factor: 91.245
Authors: Martine J Piccart-Gebhart; Marion Procter; Brian Leyland-Jones; Aron Goldhirsch; Michael Untch; Ian Smith; Luca Gianni; Jose Baselga; Richard Bell; Christian Jackisch; David Cameron; Mitch Dowsett; Carlos H Barrios; Günther Steger; Chiun-Shen Huang; Michael Andersson; Moshe Inbar; Mikhail Lichinitser; István Láng; Ulrike Nitz; Hiroji Iwata; Christoph Thomssen; Caroline Lohrisch; Thomas M Suter; Josef Rüschoff; Tamás Suto; Victoria Greatorex; Carol Ward; Carolyn Straehle; Eleanor McFadden; M Stella Dolci; Richard D Gelber Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245