Human pathology · 2026
Correlation of NPM1 immunohistochemistry with mutation subtypes, clinicopathologic variables and molecular testing in AML with NPM1 mutation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Germans Sharon Koorse, Weinberg Olga K, Chen Weina, Cantu Miguel, Chen Mingyi, Oliver Dwight, Koduru Prasad, Bigham Lindsay
Аннотация
BACKGROUND: Nucleophosmin 1 (NPM1) mutations define a major molecular subtype of acute myeloid leukemia (AML). Although RT-PCR and next-generation sequencing (NGS) remain the gold standard for diagnosis and minimal/measurable residual disease (MRD) assessment, NPM1 mutant-specific immunohistochemistry (NPM1m IHC) using monoclonal antibodies presents a rapid and cost-effective alternative. Correlation between NPM1m IHC patterns and specific NPM1 mutation subtypes remain underexplored.
OBJECTIVES: Evaluate the diagnostic utility of NPM1m IHC in AML with NPM1 mutation and to assess its correlation with mutation subtypes, morphologic features, cytogenetic profiles, co-mutations, and clinical outcomes.
METHODS: A retrospective cohort of 36 AML cases with confirmed NPM1 mutations (2018-2024) were analyzed for clinicopathologic variables, cytogenetics, PCR/NGS data, and NPM1m IHC results with subgroup analysis between Type A (n = 28) and non-Type A (n = 8) mutations.
RESULTS: NPM1m IHC positivity was observed in all insertional NPM1 mutation subtypes with two distinct staining patterns: homogeneous and two-toned, with two-toned pattern more frequent in Type A mutations. Non-Type A mutations were more often associated with complex karyotypes and showed a trend toward less frequent FLT3 co-mutations. Monocytic differentiation and cup-like nuclear morphology were assessed in both subgroups. No significant difference in survival or remission rates was observed between groups, although Type A mutations exhibited higher rates of dysplasia (p = 0.03).
CONCLUSION: NPM1m IHC is a sensitive and timely surrogate marker for insertional NPM1 mutations, correlating well with molecular results and useful in both immediate diagnosis and MRD evaluation. This study reveals subtype-specific morphologic and cytogenetic associations and highlights the need for further investigation into non-insertional NPM1 mutations and their detection challenges.
OBJECTIVES: Evaluate the diagnostic utility of NPM1m IHC in AML with NPM1 mutation and to assess its correlation with mutation subtypes, morphologic features, cytogenetic profiles, co-mutations, and clinical outcomes.
METHODS: A retrospective cohort of 36 AML cases with confirmed NPM1 mutations (2018-2024) were analyzed for clinicopathologic variables, cytogenetics, PCR/NGS data, and NPM1m IHC results with subgroup analysis between Type A (n = 28) and non-Type A (n = 8) mutations.
RESULTS: NPM1m IHC positivity was observed in all insertional NPM1 mutation subtypes with two distinct staining patterns: homogeneous and two-toned, with two-toned pattern more frequent in Type A mutations. Non-Type A mutations were more often associated with complex karyotypes and showed a trend toward less frequent FLT3 co-mutations. Monocytic differentiation and cup-like nuclear morphology were assessed in both subgroups. No significant difference in survival or remission rates was observed between groups, although Type A mutations exhibited higher rates of dysplasia (p = 0.03).
CONCLUSION: NPM1m IHC is a sensitive and timely surrogate marker for insertional NPM1 mutations, correlating well with molecular results and useful in both immediate diagnosis and MRD evaluation. This study reveals subtype-specific morphologic and cytogenetic associations and highlights the need for further investigation into non-insertional NPM1 mutations and their detection challenges.