BRAFV600E and NRASQ61L/Q61R mutation analysis in metastatic melanoma using immunohistochemistry: a study of 754 cases highlighting potential pitfalls and guidelines for interpretation and reporting. Issue 4 (15th June 2016)

• Record Type: Journal Article
• Authors: Kakavand, Hojabr; Walker, Emily; Lum, Trina; Wilmott, James S; Selinger, Christina I; Smith, Elizabeth; Saw, Robyn P M; Yu, Bing; Cooper, Wendy A; Long, Georgina V; O'Toole, Sandra A; Scolyer, Richard A
• Is Part Of: Histopathology. Volume 69:Issue 4(2016)
• Page Start: 680
• Page End: 686
• Publication Date: 2016-06-15
• Subjects: BRAF -- diagnosis -- immunohistochemistry -- melanoma -- NRAS; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12992
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Background and aims: BRAF or NRAS mutations occur in approximately 60% of cutaneous melanomas, and the identification of such mutations underpins the appropriate selection of patients who may benefit from BRAF and MEK inhibitor targeted therapies. The utility of immunohistochemistry (IHC) to detect NRAS Q61L mutations is currently unknown. This study sought to assess the sensitivity and specificity of anti‐BRAF V600E (VE1), anti‐NRAS Q61R (SP174) and anti‐NRAS Q61L (26193) antibodies for mutation detection in a large series of cases. Methods and results: Mutation status was determined using the OncoCarta assay in 754 cutaneous melanomas. IHC with the anti‐BRAF V600E antibody was performed in all cases, and the anti‐NRAS Q61R and anti‐NRAS Q61L antibodies were assessed in a subset of 302 samples utilizing tissue microarrays. The staining with the anti‐BRAF V600E and anti‐NRAS Q61R antibodies was diffuse, homogeneous and cytoplasmic. The anti‐NRAS Q61L antibody displayed variable intensity staining, ranging from weak to strong in NRAS Q61L mutant tumours. The sensitivity and specificity for anti‐BRAF V600E was 100 and 99.3%, anti‐NRAS Q61R was 100 and 100% and anti‐NRAS Q61L was 82.6 and 96.2%, respectively. Conclusions: The use of IHC is a fast, efficient and cost‐effective method to identify single specific mutations in melanoma patients. BRAF V600E and NRAS Q61R antibodies have high sensitivity and specificity; however, the NRAS Q61L antibody appears less sensitive. IHC can help to facilitate the timely, appropriate selection and treatment of metastatic melanoma patients with targeted therapies. Detection of melanoma‐associated mutations by IHC may also provide evidence for a diagnosis of melanoma in metastatic undifferentiated neoplasms lacking expression of melanoma antigens.