ArticleEndocrine pathology2024
The Potential Utility of RAS Q61R Immunohistochemistry as a Screening Tool in Pre-operative Fine Needle Aspirates of Medullary Thyroid Carcinoma.
Article in Endocrine pathology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Medullary thyroid carcinoma (MTC) can either be sporadic, often via mutually exclusive RET or RAS alterations, or inherited via a RET germline alteration. Germline testing is recommended for all patients diagnosed with MTC. RAS p.Q61R immunohistochemistry (RASQ61R-IHC) can identify a subset of RAS-mutated MTCs on resections, but whether this could be applied pre-operatively to cytology specimens remains unclear. Herein, we assessed RASQ61R-IHC in a tri-institutional cohort of cytologic and histologic MTC specimens with available molecular and germline data. Thirty-four fine needle aspirates with cell blocks were identified between three institutions from 2009 to 2024 with corresponding histology. Tumor sequencing and germline data were recorded, if available. RASQ61R-IHC was scored on staining intensity with documentation of membranous accentuation. Sensitivity, specificity, positive predictive (PPV), and negative predictive values (NPV) were calculated. Of the MTCs, 29% were germline-mutated, and 71% were sporadic. Among all sporadic MTCs (n = 22), 41% were RET-altered, 27% were RAS-altered, and 31.8% did not have available data. With any RASQ61R-IHC staining considered positive, sensitivity, specificity, PPV, and NPV for detecting RAS p.Q61R-mutated MTCs were 100%, 72.7%, 45.4%, and 100%, respectively. Requiring a stain score of > 1 and/or membranous accentuation for a true positive changed sensitivity, specificity, PPV, and NPV to 100%, 100%, 100%, and 100%, respectively. RASQ61R-IHC membranous staining was 100% predictive of RET-negative germline testing. RASQ61R-IHC, when requiring a score > 1 and/or membranous stain accentuation for true positive, had high sensitivity and specificity for RAS p.Q61R mutation in cytologic and surgical MTC specimens. Moreover, RASQ61R-IHC is a rapid and inexpensive modality that could potentially tailor which MTC patients undergo germline testing.
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