Immunohistochemistry as an accurate tool for the assessment of <i>BRAF V600E</i> and <i>TP53</i> mutations in primary and metastatic melanoma

Rusu, Ștefan; Verocq, Camille; Trépant, Anne Laure; Maris, Calliope; Nève, Nancy De; Blanchard, Oriane; Campenhout, Claude Van; Clercq, Sarah De; Rorive, Sandrine; Cotoi, Ovidiu Simion; Decaestecker, Christine; Salmon, Isabelle; D’Haene, Nicky

doi:10.3892/mco.2021.2432

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…Karbel et al [22] reported almost perfect agreement (kappa = 1.0) for BRAF VE1 IHC interpretation with three pathologists in 53 lung cancers. Previous studies on the interobserver agreement for BRAF VE1 IHC interpretation in PTCs, melanomas, and CRCs reported moderate to perfect agreement (kappa=0.554-1.0) [12][13][14][15][16][17][18][19][20]. But, in most studies, two or three pathologists interpreted the results of IHC.…”

Section: Discussionmentioning

confidence: 96%

“…The BRAF VE1 IHC was known to have a sensitivity of 86%-100% and a specificity of 93-100% in detecting BRAF V600E mutation in papillary thyroid carcinomas (PTCs), melanomas, and colorectal cancers (CRCs) with moderate to perfect interobserver agreements [3,[9][10][11][12][13][14][15][16][17][18][19][20]. Hence, National Comprehensive Cancer Network guidelines recommend the BRAF VE1 IHC as a screening test for the assessment of BRAF V600E status in melanomas and CRCs.…”

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confidence: 99%

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Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Chang

Choi

Shim

et al. 2022

JPTM

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Background: Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non-small cell lung cancers (NSCLCs). Methods: A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images. Results: In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. Conclusions: BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Chang

Choi

Shim

et al. 2022

JPTM

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“…These controversies could be resolved in an improved way with larger sample sizes. Further molecular testing of other methods, such as next-generation sequencing could also be useful, as a report of inter-method discrepancy exists ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of P53 immunostaining in patients with cutaneous melanoma

Meevassana,

Mittrakulkij,

Toworrakul

et al. 2023

Biomed Rep

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P53 is a tumor suppressor gene that is mutated in numerous types of cancer. The aim of the present study was to determine the frequency of this mutation in cutaneous melanomas and to conduct clinicopathological characteristics and clinical outcome association analyses with the P53 mutation. P53 immunohistochemical staining was used as a surrogate marker for P53 mutation analysis to assess P53 status. In the present study, 50 pathological samples of cutaneous melanoma from 2012 to 2018 at Chulalongkorn University (Bangkok, Thailand), were subjected to anti-P53 immunohistochemistry, followed by an examination of the association between P53 statuses and clinical and pathological characteristics, along with clinical outcomes. A positive staining for anti-P53 antibody was detected in 30% of patients (15/50) with cutaneous melanomas. Positivity was significantly associated with female sex, nodular histological subtype and Breslow level 4. Cox regression analysis revealed that an age >65.5 years and Breslow grade 4 disease were associated with mortality. The Kaplan-Meier curve revealed a shorter duration of recurrence time in the P53 mutation than P53 wild type. In the present study, P53 mutations in specific cases of cutaneous melanoma were identified. Notably, patients who were older and/or had a Breslow score of 4 exhibited an increased risk of mortality. These findings suggested the potential involvement of P53 mutations in cutaneous melanoma, highlighting the necessity for further investigations to improve understanding of their roles.

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“…Third, cutaneous malignant melanomas occasionally have increased or aberrant p53 expression [79]. The aberrant expression does not inevitably correlate with TP53 mutations [80], and the expression of wild-type p53 may favor melanoma [81]. Interestingly, the Spitz tumor, a distinctive nevus cell neoplasm, has been reported to have a TP53-NTRK1 fusion gene [82], but its p53 immunotypes are not yet evident.…”

Section: Tp53/p53mentioning

confidence: 99%

The Pathology according to p53 Pathway

Hatano

2023

Pathobiology

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Background Observations play a pivotal role in the progress of science, including in pathology. The cause of a disease such as cancer is analyzed by breaking it down into smaller organs, tissues, cells, and molecules. The current standard cancer diagnostic procedure, microscopic observation, relies on preserved morphological characteristics. In contrast, molecular analyses explore oncogenic pathway activation that leads to genetic mutations and aberrant protein expression. Such molecular analyses could potentially identify therapeutic targets and has gained considerable attention in clinical oncology. Summary This review summarizes the cardinal biomarkers of the p53 pathway, p53, p16, and mouse double minute 2 (MDM2), in the context of traditional surgical pathology and emerging genomic oncology. The p53 pathway, which is dysregulated in more than a half of all cancers, can be applied in several diagnostic settings. A four-classification model of immunophenotype for p53 pathway gene status, tumor types with a high frequency of abnormalities for each p53 pathway gene, and a minimal p53 pathway immunohistochemical panel is also described. Key messages Immunohistochemistry of oncogenic signals should be interpreted according to molecular findings based on genomic oncology, in addition to the microscopic findings of diagnostic pathology.

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Immunohistochemistry as an accurate tool for the assessment of BRAF V600E and TP53 mutations in primary and metastatic melanoma

Cited by 8 publications

References 45 publications

Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Evaluation of P53 immunostaining in patients with cutaneous melanoma

The Pathology according to p53 Pathway

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