title: Growth characteristics of rectal carcinoid tumors.
abstract: OBJECTIVE
  Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors.
  
  
  METHODS
  Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-alpha, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique.
  
  
  RESULTS
  The median Ki-67 labeling index (LI) in all lesions was 0.62 +/- 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-alpha was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0. 05) higher in lesions with TGF-alpha expression than in lesions without TGF-alpha expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-alpha and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 +/- 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions.
  
  
  CONCLUSIONS
  The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-alpha/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.
authors.affiliation: First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Haruma
authors.forename: Y
authors.initials: Y
authors.lastname: Kitadai
authors.forename: M
authors.initials: M
authors.lastname: Yoshihara
authors.forename: K
authors.initials: K
authors.lastname: Sumii
authors.forename: G
authors.initials: G
authors.lastname: Kajiyama
authors.forename: F
authors.initials: F
authors.lastname: Shimamoto
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016211:Transforming Growth Factor alpha; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors