title: Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical stage, PHH3, Ki-67 or mitotic indices.
abstract: Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices.
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.|Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nonaka
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Murakami
authors.affiliation: Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015266:Carcinoma, Merkel Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D059965:Merkel cell polyomavirus; D008875:Middle Aged; D008938:Mitosis / Q000502:physiology*; D009367:Neoplasm Staging; D010766:Phosphorylation; D027601:Polyomavirus Infections / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D019394:Ki-67 Antigen
keywords: Ki-67; Merkel cell carcinoma; Merkel cell polyomavirus; PHH3; mitotic index; phosphohistone-H3