title: Papillary microcarcinomas of the thyroid with preoperatively detectable lymph node metastasis show significantly higher aggressive characteristics on immunohistochemical examination.
abstract: OBJECTIVE
  We recently demonstrated that papillary microcarcinomas with preoperatively detectable node metastasis in the lateral compartment on ultrasonography (clinically apparent metastasis) show worse postoperative relapse-free survival than those with no metastasis or metastasis that could not be detected preoperatively, but was confirmed by pathological examination after surgery (occult metastasis). In this study, we investigated difference in the aggressive characteristics of microcarcinoma of this type from various perspectives.
  
  
  METHODS
  We immunohistochemically examined the expression of cell proliferating markers, Ki-67, cyclin D1, p27, and retinoblastoma gene product (pRb), apoptotic markers, single-strand DNA (ssDNA), and metastatic suppressor, kangai-1 (KAI-1) for 19 microcarcinoma patients with clinically apparent metastasis, 14 patents with occult metastasis, and 22 patients without metastasis.
  
  
  RESULTS
  Cases of clinically apparent metastasis showed increased cyclin D1 expression together with decreased p27 expression and higher levels of pRb and Ki-67 expression. Furthermore, ssDNA expression was higher and bcl-2 expression was lower in these cases, while KAI-1 expression was significantly reduced. There was no significant difference in the expression of these proteins between cases demonstrating no and occult metastases.
  
  
  CONCLUSIONS
  These findings suggest that cases of clinically apparent metastasis show significantly higher growth based on cell proliferating activity, apoptosis, and expression of metastatic suppressor than those demonstrating no or occult metastases.
authors.affiliation: Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-Dori, Chuo-ku, Kobe City, Japan. ito01@kuma-h.or.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Uruno
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzuka
authors.forename: Kanji
authors.initials: K
authors.lastname: Kuma
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000032:analysis; D019938:Cyclin D1 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004277:DNA, Single-Stranded / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis; D014463:Ultrasonography
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C497688:CD82 protein, human; D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D051861:Kangai-1 Protein; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27