title: Contradictory KRAS mutation test results in a patient with metastatic colon cancer: a clinical dilemma in the era of personalized medicine.
abstract: The KRAS oncogene is mutated in 40‒50% of colorectal cancers and confers resistance to EGFR-targeted therapy. In the clinic, agents such as cetuximab or panitumumab target the EGFR receptor for therapeutic benefit. Cetuximab was approved by the FDA in 2012 as first-line therapy for KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer, in combination with FOLFIRI (5-fluorouracil, irinotecan, leucovorin). Herein we report a case of metastatic colon cancer with conflicting testing results for the KRAS oncogene from two different reference laboratories. The discordant reports complicated the decision-making process regarding the administration of targeted anti-EGFR personalized therapy. As the second test result was wild-type from the same original pathological specimen, the patient was treated with cetuximab-containing combination chemotherapy and appeared to have a response after prior disease progression. It is unclear whether the observed response was fully due to regression of wild-type KRAS-containing tumor or any component of antibody-dependent cellular cytotoxicity to a heterogeneous tumor in this patient.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA USA. nlamparella@hmc.psu.edu
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Lamparella
authors.forename: Bikramajit S
authors.initials: BS
authors.lastname: Saroya
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.forename: Nabeel E
authors.initials: NE
authors.lastname: Sarwani
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D057285:Precision Medicine / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: KRAS mutation; cetuximab; colon cancer; targeted therapy; tumor heterogeneity