ABSTRACT
Intraductal papillary neoplasm of bile duct (IPNB) is one of the precursor lesions of cholangiocarcinoma. Although hepatolithiasis has been extensively studied in its association with IPNBs, there had been no comprehensive study of IPNBs with Clonorchis sinensis infection. Twelve IPNBs were selected from 20 surgically resected cholangiocarcinomas, positive for C. sinensis tests (60%) and compared with eight IPNBs, selected from 51 resected cholangiocarcinomas, negative for C. sinensis tests (16%), by histologic and immunohistochemical studies of mucin core proteins and cytokeratin panels. The predominant immuno-phenotype of IPNB cases with Clonorchiasis was pancreatobiliary type (MUC1+/MUC2-/CDX2-; 9/12 cases), while that of IPNB cases with negative for C. sinensis was intestinal type (MUC1-/MUC2+/CDX2+; 6/8; p = 0.04). The prevalence of IPNBs was higher when patients with cholangiocarcinoma had Clonorchiasis. IPNBs with Clonorchiasis tended to have a more pancreatobiliary phenotype, which suggests IPNBs with Clonorchiasis may have a different tumorigenesis pathway from IPNBs with other etiologies.
Subject(s)
Bile Duct Neoplasms/parasitology , Bile Ducts, Intrahepatic , Cholangiocarcinoma/parasitology , Clonorchiasis/complications , Aged , Animals , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/metabolism , CDX2 Transcription Factor , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/metabolism , Clonorchiasis/diagnosis , Clonorchiasis/metabolism , Clonorchis sinensis , Female , Homeodomain Proteins/metabolism , Humans , Liver/metabolism , Liver/parasitology , Male , Middle Aged , Mucin 5AC , Mucin-1/metabolism , Mucin-2/metabolism , Retrospective StudiesABSTRACT
Aberrant expression of Sonic hedgehog (Shh) has been reported in many human cancers including ductal carcinoma of the pancreas. The intraductal papillary mucinous tumor (IPMT) has been considered as one of the precursor lesions of invasive ductal carcinoma of the pancreas. Shh expression in pancreatic IPMT has not been reported. We investigated an immunohistochemical (IHC) expression of Shh in 55 cases of pancreatic IPMT. We analyzed the IHC expression of Shh in the following histologic grades of tumor: adenoma (AD), moderate dysplasia (MD), noninvasive carcinoma (NIC), and invasive carcinoma (IC), and with the following histologic subtype classification: intestinal, pancreatobiliary, null, and unclassifiable type. IHC Shh expression was noted in 6 (46.2%) of 13 AD, 5 (35.7%) of 14 MD, 12 (80%) of 15 NIC, and 11 (84.6%) of 13 IC. Shh expression was significantly increased in malignant IPMT (NIC+IC) compared with nonmalignant IPMT (AD+MD) (82.1% vs. 40.7%, P=0.0005). IHC Shh expression was found in 11 (68.8%) of 16 intestinal types, 13 (92.8%) of 14 pancreatobiliary types, 8 (38.1%) of 21 null types, and 2 (50%) of 4 unclassifiable types. Intestinal and pancreatobiliary subtypes showed a high expression of Shh compared with the null and unclassifiable type of IPMT. All 3 cases of node metastasis showed IHC Shh expression in tumor cells of metastatic lymph nodes. Therefore, Shh expression may have a critical role in the late stage of carcinogenesis of IPMT, and may impact metastatic progression to the lymph nodes in malignant IPMT.
Subject(s)
Adenocarcinoma, Mucinous/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Papillary/pathology , Hedgehog Proteins/metabolism , Pancreatic Neoplasms/pathology , Adenocarcinoma, Mucinous/chemistry , Adenocarcinoma, Mucinous/metabolism , Carcinoma, Intraductal, Noninfiltrating/chemistry , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Papillary/chemistry , Carcinoma, Papillary/metabolism , Female , Hedgehog Proteins/analysis , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Neoplasm Invasiveness , Pancreatic Neoplasms/chemistry , Pancreatic Neoplasms/metabolism , Survival AnalysisABSTRACT
BACKGROUND: Little information is available about the familial aggregation of inflammatory bowel disease (IBD) in Asian populations. We therefore determined the risk of familial aggregation of IBD among first-degree relatives of patients with ulcerative colitis (UC) or Crohn's disease (CD) in an ethnically distinct Korean population. METHODS: Familial aggregation of IBD was evaluated in terms of family history, prevalence, lifetime risk, and population relative risk in first-degree relatives of 1440 unrelated patients with UC (n = 1043) or CD (n = 397). RESULTS: A positive first-degree family history of IBD was observed in 27 probands (1.88%): 21 of 1043 (2.01%) with UC and 6 of 397 (1.51%) with CD. The crude prevalence of IBD in first-degree relatives of probands with IBD was 0.31%. The lifetime risk of IBD was 0.54% in all first-degree relatives of IBD probands, 0.52% in UC probands, and 0.67% in CD probands, with overall lifetime relative risks of 0.12% in parents, 0.79% in siblings, and 1.43% in offspring. The age- and sex-adjusted population relative risk of IBD was 13.8 in first-degree relatives of probands with IBD. CONCLUSIONS: Although a positive family history, prevalence, and lifetime risk of IBD among first-degree relatives of Korean IBD patients are much lower than among relatives of Western patients, the population relative risk in first-degree relatives is about equal in Koreans and Westerners. This finding indicates that a positive family history is an important risk factor for IBD in Koreans and in Westerners.
