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Pancreatic Intraepithelial Neoplasia (pancreatic + intraepithelial_neoplasia)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas

GENES TO CELLS, Issue 7 2008
Tetsu Yoshida
Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas. [source]

Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2006
Kenoki Ohuchida
Abstract Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When ,-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer. © 2005 Wiley-Liss, Inc. [source]

Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survival

CANCER, Issue 3 2006
Evan Matros M.D.
Abstract BACKGROUND Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Application of this principle to a single malignancy may identify cancer subtypes with altered developmental programs. Herein, we investigate the relevance of two widely used cytokeratins (CKs), 7 and 20, to subtype pancreas cancer and identify associations with clinical features. METHODS A tissue microarray was constructed using tumor specimens from 103 patients who underwent resection for pancreatic adenocarcinoma with curative intent. A subset of resection specimens was evaluated for pancreatic intraepithelial neoplasia (PanIN) lesions. Tissues were immunostained by using specific anticytokeratin 7 and 20 monoclonal antibodies. RESULTS CK 7 and 20 expression was present in 96% and 63% cases of pancreatic adenocarcinoma, respectively. Ubiquitous CK 7 expression precluded further analysis. Tumoral CK 20 expression was not associated with any histopathologic parameter but correlated with worse prognosis when considered as either a dichotomous (P = 0.0098) or continuous (P = 0.007) variable. In a multivariate model, tumoral CK 20 expression remained a significant independent prognosticator. CK 20 expression was absent in all PanIN lesions from eight resection specimens in which the tumor component was negative for CK 20. In contrast, presence of tumoral CK 20 was highly concordant with its expression in corresponding PanINs. CONCLUSIONS CK 20 expression defines a subtype of pancreas cancer with important biologic properties. When present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions. Further studies to identify the underlying genetic changes associated with this altered developmental pathway are warranted. Cancer 2006. © 2005 American Cancer Society. [source]

Molecular mechanisms of pancreatic carcinogenesis

CANCER SCIENCE, Issue 1 2006
Toru Furukawa
Pancreatic ductal adenocarcinoma is one of the most fatal malignancies. Intensive investigation of molecular pathogenesis might lead to identifying useful molecules for diagnosis and treatment of the disease. Pancreatic ductal adenocarcinoma harbors complicated aberrations of alleles including losses of 1p, 6q, 9p, 12q, 17p, 18q, and 21q, and gains of 8q and 20q. Pancreatic cancer is usually initiated by mutation of KRAS and aberrant expression of SHH. Overexpression of AURKA mapping on 20q13.2 may significantly enhance overt tumorigenesity. Aberrations of tumor suppressor genes synergistically accelerate progression of the carcinogenic pathway through pancreatic intraepithelial neoplasia (PanIN) to invasive ductal adenocarcinoma. Abrogation of CDKN2A occurs in low-grade/early PanIN, whereas aberrations of TP53 and SMAD4 occur in high-grade/late PanIN. SMAD4 may play suppressive roles in tumorigenesis by inhibition of angiogenesis. Loss of 18q precedes SMAD4 inactivation, and restoration of chromosome 18 in pancreatic cancer cells results in tumor suppressive phenotypes regardless of SMAD4 status, indicating the possible existence of a tumor suppressor gene(s) other than SMAD4 on 18q. DUSP6 at 12q21-q22 is frequently abrogated by loss of expression in invasive ductal adenocarcinomas despite fairly preserved expression in PanIN, which suggests that DUSP6 works as a tumor suppressor in pancreatic carcinogenesis. Restoration of chromosome 12 also suppresses growths of pancreatic cancer cells despite the recovery of expression of DUSP6; the existence of yet another tumor suppressor gene on 12q is strongly suggested. Understanding the molecular mechanisms of pancreatic carcinogenesis will likely provide novel clues for preventing, detecting, and ultimately curing this life-threatening disease. (Cancer Sci 2005) [source]