Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma
Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS -mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated...
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Veröffentlicht in: | Modern pathology 2015-04, Vol.28 (4), p.487-497 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Testing for
NRAS
is now integral part in the assessment of metastatic melanoma patients because there is evidence that
NRAS
-mutated patients may be sensitive to MEK inhibitors, and
RAS
mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the
NRASQ61R
mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of
NRAS
mutation were retrieved from a multicentric database. Formalin-fixed and paraffin-embedded melanoma tissues were analyzed for
BRAF
and
NRAS
mutations by independent, blinded observers using both conventional DNA molecular techniques and immunohistochemistry with the novel anti-human N-Ras (Q61R) monoclonal antibody (clone SP174). The antibody showed a sensitivity of 100% (14/14) and a specificity of 100% (83/83) for detecting the presence of an
NRASQ61R
mutation. Of the
NRAS
-mutated cases, none of the non-
Q61R
cases stained positive with the antibody (0/7). There were three cases with discordant
NRAS
mutational results. Additional molecular analysis confirmed the immunohistochemically obtained
NRAS
result in all cases, suggesting that a multiple analytical approach can be required to reach the correct sample classification. The reported immunohistochemical method is an accurate, rapid, and cost-effective method for detecting
NRASQ61R
mutation in melanoma patients, and represents a valuable supplement to traditional mutation testing. If validated in further studies, genetic testing would only be required for immunohistochemistry-negative patients to detect non-
Q61R
mutations. |
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ISSN: | 0893-3952 1530-0285 |
DOI: | 10.1038/modpathol.2014.137 |