title: Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load.
abstract: Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis.
authors.affiliation: Department of Pathology, Faculty of Medicine, Robert Debré University Hospital, 51092 Reims, France. Electronic address: lerouxvaleri@gmail.com.
authors.forename: Valérie
authors.initials: V
authors.lastname: Leroux-Kozal
authors.affiliation: Clinical and Molecular Virology Unit, University Hospital, 51092 Reims, France; Faculty of Medicine, EA-4684 Cardiovir SFR-CAP Santé, 51092 Reims, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévêque
authors.affiliation: Clinical and Molecular Virology Unit, University Hospital, 51092 Reims, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Brodard
authors.affiliation: Department of Dermatology, Robert Debré University Hospital, 51092 Reims, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Lesage
authors.affiliation: Department of Pathology, Faculty of Medicine, Robert Debré University Hospital, 51092 Reims, France.
authors.forename: Oriane
authors.initials: O
authors.lastname: Dudez
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Robert Debré University Hospital, 51092 Reims, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Makeieff
authors.affiliation: Department of Research and Innovation, Robert Debré University Hospital, 51092 Reims, France.
authors.forename: Lukshe
authors.initials: L
authors.lastname: Kanagaratnam
authors.affiliation: Department of Pathology, Faculty of Medicine, Robert Debré University Hospital, 51092 Reims, France.
authors.forename: Marie-Danièle
authors.initials: MD
authors.lastname: Diebold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000952:Antigens, Polyomavirus Transforming / Q000302:isolation & purification*; D014408:Biomarkers, Tumor / Q000302:isolation & purification*; D001706:Biopsy; D015266:Carcinoma, Merkel Cell / Q000737:chemistry / Q000453:epidemiology / Q000473:pathology* / Q000556:secondary / Q000821:virology*; D015897:Comorbidity; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D018862:Merkel Cells / Q000737:chemistry / Q000473:pathology / Q000821:virology; D059965:Merkel cell polyomavirus / Q000302:isolation & purification; D008875:Middle Aged; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology; D011379:Prognosis; D012878:Skin Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D019562:Viral Load
chemical_list: D000952:Antigens, Polyomavirus Transforming; D014408:Biomarkers, Tumor
keywords: Histopathologic characteristics; Immunohistochemistry; Merkel cell carcinoma; Merkel cell polyomavirus; Polymerase chain reaction; Prognosis