American Association for Cancer Research
ccr-23-0859_supplementary_figure_s1_suppfs1.pdf (212.74 kB)

Supplementary Figure S1 from Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer

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posted on 2023-10-13, 07:40 authored by Christopher J.M. Williams, Faye Elliott, Nancy Sapanara, Faranak Aghaei, Liping Zhang, Andrea Muranyi, Dongyao Yan, Isaac Bai, Zuo Zhao, Michael Shires, Henry M. Wood, Susan D. Richman, Gemma Hemmings, Michael Hale, Daniel Bottomley, Leanne Galvin, Caroline Cartlidge, Sarah Dance, Chris M. Bacon, Laura Mansfield, Kathe Young-Zvandasara, Ajay Sudan, Katy Lambert, Irena Bibby, Sarah E. Coupland, Amir Montazeri, Natalie Kipling, Kathryn Hughes, Simon S. Cross, Alice Dewdney, Leanne Pheasey, Cathryn Leng, Tatenda Gochera, D. Chas Mangham, Mark Saunders, Martin Pritchard, Helen Stott, Abhik Mukherjee, Mohammad Ilyas, Rafael Silverman, Georgina Hyland, Declan Sculthorpe, Kirsty Thornton, Imogen Gould, Ann O'Callaghan, Nicholas Brown, Samantha Turnbull, Lisa Shaw, Matthew T. Seymour, Nicholas P. West, Jenny F. Seligmann, Shalini Singh, Kandavel Shanmugam, Philip Quirke

Example AREG and EREG immunohistochemistry


UK Research and Innovation (UKRI)

Yorkshire Cancer Research (YCR)



High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56–0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50–0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice.See related commentary by Randon and Pietrantonio, p. 4021

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