| Autor: |
Turchini, John, Andrici, Juliana, Sioson, Loretta, Clarkson, Adele, Watson, Nicole, Toon, Christopher W., Shepherd, Phillip, Ng, Daniel, Dixon-McIver, Amanda, Oei, Paul, Gill, Anthony J. |
| Zdroj: |
Applied Immunohistochemistry & Molecular Morphology; August 2017, Vol. 25 Issue: 7 p475-480, 6p |
| Abstrakt: |
Anti–epidermal growth factor receptor–targeted therapy is only indicated in RASwild-type colorectal carcinomas (CRCs). It is recommended that both NRASand KRASmutation testing to be performed before a CRC is considered RAS wild-type. Given that mutation-specific immunohistochemistry (IHC) has been shown to be sensitive and specific for the detection of NRASQ61Rmutations in melanoma, we assessed the specificity of NRASQ61Rmutation-specific IHC in CRC. IHC was performed on tissue microarrays containing 2823 consecutive CRC undergoing surgery with curative intent using a novel mutation-specific antibody to the protein produced by the NRASQ61Rmutation (clone SP174). Tissue microarrays were assessed by 2 observers and all IHC-positive or equivocal cases were repeated on whole sections to confirm the result. Positive cases then underwent molecular testing by matrix-assisted laser desorption/ionization-time of flight polymerase chain reaction. In total, 22 of 2823 (0.8%) CRCs demonstrated confirmed positive staining with complete interobserver concordance. RASmutations were confirmed in all IHC-positive CRCs. In total, 11 cases harbored the NRASQ61Rmutation. Surprisingly, 11 cases demonstrated the KRASQ61Rmutation. We conclude that mutation-specific IHC with this currently available NRASQ61R antibody is highly specific for the presence of either NRASQ61Ror KRASQ61Rmutations in CRC. We caution that we did not assess the sensitivity of IHC and that this antibody does not detect other RASmutations. Therefore, negative staining does not exclude a clinically significant RAS mutation. However, positive staining confirms the presence of an NRASQ61Ror KRASQ61Rmutation without the need for further molecular testing. |
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