title: Well-differentiated pancreatic ductal adenocarcinomas measuring ≤ 1 cm exhibit early features of tumor progression: a report of five lesions and a comparative study with advanced lesions.
abstract: OBJECTIVE
  The purpose of this study was to clarify whether the features of well-differentiated pancreatic ductal adenocarcinomas (PDACs) measuring ≤ 1 cm are the same as those of early PDACs.
  
  
  METHODS
  Five well-differentiated PDACs measuring ≤ 1 cm were clinicopathologically compared with 19 ≥ 2 cm PDACs. Additionally, an immunohistochemical analysis for abnormalities in the expression of five molecular parameters: MUC1, p16, p53, Smad4 and sonic hedgehog, which are associated with tumor progression, was performed.
  
  
  RESULTS
  The clinicopathological comparison revealed that well-differentiated PDACs measuring ≤ 1 cm were detected significantly more often without angiolymphatic invasion and with a sparse presence of cancer cells than were the ≥ 2 cm PDACs. On the other hand, in well-differentiated PDACs measuring ≤ 1 cm, the incidence of abnormal immunolabeling for MUC1, p16, p53 and sonic hedgehog was similar to that in ≥ 2 cm PDACs. However, the incidence of diffusely positive immunolabeling for MUC1 and the mean number of abnormally immunolabeled samples for the five parameters were significantly lower in well-differentiated ≤ 1 cm PDACs (20 % and 3 ± 1) than in ≥ 2 cm PDACs (90 % and 4 ± 1).
  
  
  CONCLUSIONS
  The current study revealed that as the tumor size increases, molecular abnormalities are accumulated, suggesting that well-differentiated PDACs measuring ≤ 1 cm are in an earlier stage of genetic progression than are ≥ 2 cm PDACs, and these lesions may exhibit early features of invasive PDACs.
authors.affiliation: Department of Gastroenterological Surgery, Kagawa Prefectural Central Hospital, 5-4-16 Banchou, Takamatsu, Kagawa, 760-8557, Japan, s-izumi@chp-kagawa.jp.
authors.forename: Sadanobu
authors.initials: S
authors.lastname: Izumi
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shohei
authors.initials: S
authors.lastname: Mano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Onoda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053823:Hedgehog Proteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009363:Neoplasm Proteins; C509239:SHH protein, human; D016159:Tumor Suppressor Protein p53