title: A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases.
abstract: OBJECTIVE
  High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker.
  
  
  METHODS
  Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections.
  
  
  RESULTS
  In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%).
  
  
  CONCLUSIONS
  This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.
authors.affiliation: Division of Gynecology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan. Electronic address: s.kuji@scchr.jp.
authors.forename: Shiho
authors.initials: S
authors.lastname: Kuji
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan; Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, ChuO-ku, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, Japan; Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Division of Gynecology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hirashima
authors.affiliation: Division of Gynecology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Takekuma
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ito
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, Japan; Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagashio
authors.affiliation: Division of Clinical Research Center, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Omae
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kameya
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000175:diagnosis*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000235:genetics; D012097:Repressor Proteins / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C087342:INSM1 protein, human
keywords: Cervical cancer; Human papillomavirus; INSM1; Insulinoma associated protein 1; Neuroendocrine carcinoma; Small cell carcinoma