Analysis of ASCL1/NEUROD1/POU2F3/YAP1 Yields Novel Insights for the Diagnosis of Olfactory Neuroblastoma and Identifies Sinonasal Tuft Cell-like Carcinoma.

Autor:	Febres-Aldana CA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Elsayad MM; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Saliba M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Bhanot U; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Ntiamoah P; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Takeyama A; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Purgina BM; Department of Pathology and Laboratory Medicine, Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8L6, Canada., Rodriguez-Urrego PA; Department of Pathology, University Hospital of the Santa Fe de Bogotá Medical Foundation, Bogota, 110111, Colombia., Marusic Z; Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000, Croatia., Jakovcevic A; Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000, Croatia., Chute DJ; Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195 USA., Dunn LA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Ganly I; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Cohen MA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Pfister DG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Ghossein RA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Baine MK; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Rekhtman N; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Dogan S; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. Electronic address: dogans@mskcc.org.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 Nov 27, pp. 100674. Date of Electronic Publication: 2024 Nov 27.
DOI:	10.1016/j.modpat.2024.100674
Abstrakt:	The diagnosis and treatment of sinonasal small round epithelial/neuroepithelial malignancies depends on the expression of conventional neuroendocrine markers (cNEM), such as synaptophysin, chromogranin-A, INSM1, and CD56/NCAM1. However, these tumors remain diagnostically challenging due to overlapping histologic and immunohistochemical features. The transcriptional regulators ASLC1, NEUROD1, POU2F3 and YAP1 are novel NEM (nNEM) used for subtyping of small-cell lung cancer (SCLC). Herein, we assessed the immunoexpression of nNEM in 76 sinonasal malignancies including 27 olfactory neuroblastomas (ONB), 14 small-cell (SCNEC) and 2 large-cell neuroendocrine carcinomas (LCNEC), 12 sinonasal undifferentiated carcinomas (SNUC), 7 olfactory carcinomas (OC), 11 SWI/SNF-deficient carcinomas, and 3 neuroendocrine tumors (NET). We correlated nNEM expression with the extent of neuroendocrine differentiation defined by averaged cNEM expression (NE-high: H-score≥150, NE-low: H-score<150). Dominant NE subtypes were defined by the nNEM with the highest H-score. Co-expression of two nNEM with <100 H-score difference defined a co-dominant NE subtype. NE differentiation positively correlated with NEUROD1 and negatively with YAP1 expression (p<0.0001). ONB were NE-high (96%) and all were NEUROD1-dominant/POU2F3-negative/ASCL1-negative(low)/YAP1-negative(low). In contrast to ONB, all OC were NE-low, mostly (71%) co-dominant subtypes, and NEUROD1-low(negative) (100%, p=0.0001) and YAP1-high (71%, p=0.0001). Most notably, all SNUC were POU2F3-(co)dominant/NEUROD1-negative irrespective of the IDH2 mutations. Sinonasal tumors with high POU2F3 expression showed enrichment for "tuft cell carcinoma" and tuft cell signatures (p=0.009). Similar to SCLC, SCNEC was heterogeneous in terms of nNEM expression comprising several molecular subtypes including ASCL1-(co)dominant (43%) cases. All SWI/SNF-deficient carcinomas were consistently ASLC1/NEUROD1/POU2F3-negative and YAP1-positive. ASLC1/NEUROD1/POU2F3/YAP1 are useful markers in differential diagnosis of ONB, SNUC, OC and SWI/SNF-deficient carcinomas. Subsets of SNUC and LCNEC may represent tuft cell-like carcinomas suggesting that the tuft cell could be explored as the cell of origin for these tumors. The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu