RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma.

Autor: DeCoste RC; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada. ryan.decoste@dal.ca.; Department of Pathology, Dalhousie University, Halifax, NS, Canada. ryan.decoste@dal.ca., Walsh NM; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada.; Department of Pathology, Dalhousie University, Halifax, NS, Canada.; Department of Medicine, Dalhousie University, Halifax, NS, Canada., Gaston D; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada.; Department of Pathology, Dalhousie University, Halifax, NS, Canada., Ly TY; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada.; Department of Pathology, Dalhousie University, Halifax, NS, Canada., Pasternak S; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada.; Department of Pathology, Dalhousie University, Halifax, NS, Canada., Cutler S; Department of Pathology, Dalhousie University, Halifax, NS, Canada., Nightingale M; Department of Pathology, Dalhousie University, Halifax, NS, Canada., Carter MD; Department of Pathology and Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada.; Department of Pathology, Dalhousie University, Halifax, NS, Canada.
Jazyk: angličtina
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2022 Dec; Vol. 35 (12), pp. 1829-1836. Date of Electronic Publication: 2022 Sep 08.
DOI: 10.1038/s41379-022-01151-2
Abstrakt: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine (NE) carcinoma arising from integration of Merkel cell polyomavirus (MCPyV) DNA into a host cell or from ultraviolet light-induced genetic damage (proportions vary geographically). Tumors in the latter group include those with "pure" NE phenotype and those "combined" with other elements, most often squamous cell carcinoma (SCC). We performed comprehensive genomic profiling (CGP) of MCPyV+ and MCPyV- (pure and combined) tumors, to better understand their mutational profiles and shed light on their pathogenesis. Supplemental immunohistochemistry for Rb expression was also undertaken. After eliminating low quality samples, 37 tumors were successfully analyzed (14 MCPyV+, 8 pure MCPyV- and 15 combined MCPyV-). The SCC and NE components were sequenced separately in 5 combined tumors. Tumor mutational burden was lower in MCPyV+ tumors (mean 1.66 vs. 29.9/Mb, P < 0.0001). MCPyV- tumors featured frequent mutations in TP53 (95.6%), RB1 (87%), and NOTCH family genes (95.6%). No recurrently mutated genes were identified in MCPyV+ tumors. Mutational overlap in the NE and SCC components of combined tumors was substantial ('similarity index' >24% in 4/5 cases). Loss of Rb expression correlated with RB1 mutational (P < 0.0001) and MCPyV- status (P < 0.0001) in MCCs and it was observed more frequently in the SCC component of combined MCC than in a control group of conventional cutaneous SCC (P = 0.0002). Our results (i) support existing evidence that MCPyV+ and MCPyV- MCCs are pathogenetically distinct entities (ii) concur with earlier studies linking the NE and SCC components of combined MCCs via shared genetic profiles and (iii) lend credence to the proposal that an Rb-deficient subset of SCC's is the source of phenotypically divergent combined MCCs.
(© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)
Databáze: MEDLINE
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