Validity of immunohistochemistry (IHC) to detect KRAS G12D mutations
Research type
Research Study
Full title
Validity of immunohistochemistry (IHC) to detect KRAS G12D mutations as an alternative to molecular testing in colorectal carcinomas.
IRAS ID
305453
Contact name
Ana Raquel Lobo da Rocha
Contact email
Sponsor organisation
University of Greenwich
Duration of Study in the UK
0 years, 6 months, 1 days
Research summary
Research Summary
Colorectal cancer was the fourth most incident cancer (19.5%) and the third most deadly cancer (9%) in the World in 2020.
Patients diagnosed with metastatic colorectal cancer can receive anti–EGFR targeted therapy but their response to the treatment depends on the mutational status of RAS and BRAF genes. KRAS mutations occurs in approximately 30% and 34% of cancers of the colon and rectum, respectively. The most frequent KRAS mutation in colorectal cancer is G12D, followed by G12V and G13D.
Currently, molecular techniques are the reference standard method to detect the RAS and BRAF mutations in colorectal carcinoma. Several studies tested and validated the use of a monoclonal antibody (clone VE1) for BRAF-V600E mutations in colorectal with good concordance between immunohistochemistry (IHC) and molecular tests. Thus, immunohistochemistry could be a possible alternative to molecular testing by using antibodies targeting the mutated proteins. Immunohistochemistry is present in most of the Histopathology laboratories; it does not require additional equipment or expertise and it has a shorter turnaround time than molecular testing.
The major aim of this study is to compare IHC, using a KRAS anti-G12D antibody, with molecular testing for the detection of KRAS G12D mutation, and evaluate the validity of IHC as an alternative to molecular testing in colorectal carcinomas (mCRC). Archival formalin-fixed, paraffin-embedded (FFPE) tissues from 100 patients, diagnosed with metastatic colorectal carcinoma and previously tested for KRAS mutations by molecular technique, will be tested.
The research will take place at the Histopathology department at York and Scarborough Teaching Hospitals NHS Foundation Trust during a maximum period of 6 months and it will be financially supported by the Histopathology department.Summary of Results
This study failed to detect K-Ras mutated protein. All the cases known to be positive for the KRAS mutation by molecular techniques were negative when tested with the anti-Ras antibody. Contrarily, a negative case by molecular techniques was positively stained by the anti-Ras antibody. Based on these results, immunohistochemistry is not a reliable alternative to molecular techniques in detecting KRAS mutations in colorectal cancer.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
22/YH/0026
Date of REC Opinion
17 Feb 2022
REC opinion
Favourable Opinion