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.

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma / Massi, D; Simi, L; Sensi, E; Baroni, G; Xue, G; Scatena, C; Caldarella, A; Pinzani, P; Fontanini, G; Carobbio, A; Urso, C; Mandala, M. - In: MODERN PATHOLOGY. - ISSN 0893-3952. - 28:4(2015), pp. 487-497. [10.1038/modpathol.2014.137]

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma

Carobbio A;
2015

Abstract

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.
2015
28
4
487
497
Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma / Massi, D; Simi, L; Sensi, E; Baroni, G; Xue, G; Scatena, C; Caldarella, A; Pinzani, P; Fontanini, G; Carobbio, A; Urso, C; Mandala, M. - In: MODERN PATHOLOGY. - ISSN 0893-3952. - 28:4(2015), pp. 487-497. [10.1038/modpathol.2014.137]
Massi, D; Simi, L; Sensi, E; Baroni, G; Xue, G; Scatena, C; Caldarella, A; Pinzani, P; Fontanini, G; Carobbio, A; Urso, C; Mandala, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1331607
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