Felisiak-Golabek et al., "SP174
, NRAS Q61R mutant-specific antibody, cross-reacts with KRAS Q61R mutant protein in colorectal carcinoma," Archives of Pathology & Laboratory Medicine, vol.
To the Editor.--Lasota et al (1) recently reported further data about the high sensitivity of SP174 immunohistochemistry in the detection of RASQ61R mutants in colorectal carcinomas.
In addition to NRASQ61R and KRASQ61R, high sensitivity was also recently reported with SP174 immunohistochemistry in a subset of thyroid medullary carcinomas to detect HRASQ61R mutations in triaging genetic testing for type 2 multiple endocrine neoplasia syndrome.
Nevertheless, RASQ61R variants represent only about 1% of these mutations, and screening for these variants in routine SP174 testing could avoid analyses in only 1% of cases.
Given the frequency of NRASQ61R mutation in melanomas, contrary to the situation with thyroid and colorectal cancers, we believe that SP174 immunohistochemistry could be a valuable test in melanoma and could avoid about 10% of DNA-based molecular analyses in cases of SP174-positive analyses.
In addition to previous studies dedicated to VE1 anti-BRAF V600E immunohistochemistry, further studies are needed to determine the medicoeconomic usefulness of implementing SP174 anti-RASQ61R immunohistochemistry in routine practice.
(4,5) Recently, a rabbit monoclonal antibody (clone SP174) against NRAS Q61R mutant protein has been made commercially available.
Expression of the NRAS Q61R mutant protein was evaluated immunohistochemically by using a rabbit monoclonal antibody, clone SP174 (Spring Bioscience, Pleasanton, California).
Screening of 1185 colorectal carcinomas revealed 12 tumors (in 1 case primary and metastatic lesion) with immunoreactivity to SP174, NRAS Q61R mutant-specific antibody.
None of the NRAS/KRAS wild-type tumors and NRAS/KRAS mutants other than Q61R showed immunoreactivity with SP174 antibody.
This study revealed that immunohistochemistry with SP174 antibody did not allow identification of NRAS Q61R versus KRAS Q61R mutant protein.
This study showed that immunohistochemistry with SP174 antibody allowed identification of KRAS and NRAS Q61R mutant proteins.