Case report: Intraductal tubulopapillary neoplasm of the pancreas with unique clear cell phenotype.

Unlabelled: Intraductal tubulopapillary neoplasms of the pancreas are very rare tumors characterized by intraductal tubulopapillary growth, ductal differentiation, scant intracellular mucin production and cellular dysplasia. Here, we report the first case of an intraductal tubulopapillary neoplasm of the pancreas with clear cell morphology. The tumor was detected during the diagnostic work-up of acute pancreatitis in a 43- year old female.

Manual microdissection combined with antisense RNA-longSAGE for the analysis of limited cell numbers.

Establishing a gene expression profile of defined subtypes of cells within an organ is still challenging because it frequently requires microdissection and subsequent amplification of the limited amount of messenger RNA (mRNA) isolated from the microdissected tissue in order to be able to proceed with comprehensive gene expression analyses via microarray or serial analysis of gene expression (SAGE) technology. Here we describe a manual microdissection strategy for the isolation of high-quality RNA. Furthermore, a strategy for combining linear amplification of RNA with longSAGE is described that allows the use of antisense RNA (aRNA) generated via the well-established linear amplification of RNA procedure together with the conventional SAGE or longSAGE technology.

Analysis of the pancreatic tumor progression by a quantitative proteomic approach and immunhistochemical validation.

To increase the knowledge about the development of pancreatic ductal adenocarcinoma, (PDAC) detailed analysis of the tumor progression is required. To identify proteins differentially expressed in the pancreatic intraepithelial neoplasia (PanIN), the precursor lesions of PDAC, we conducted a quantitative proteome study on microdissected PanIN cells. Proteins from 1000 microdissected cells were subjected to a procedure combining fluorescence dye saturation labeling with high resolution two-dimensional gel electrophoresis (2-DE).

Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues.

Background: MicroRNAs (miRNAs) are RNA molecules that are involved in the regulation of many cellular processes, including those related to human cancers. The aim of this study was to determine, as a proof of principle, whether specific candidate miRNAs could be detected in fine-needle aspirate (FNA) biopsies of pancreatic ductal adenocarcinoma (PDAC) and could accurately differentiate malignant from benign pancreatic tissues.

Methods: We used TaqMan(R) assays to quantify miRNA levels in FNA samples collected in RNARetain (n = 16) and compared the results with a training set consisting of frozen macrodissected pancreatic samples (n = 20).

Aberrant expression of a disintegrin and metalloproteinase 17/tumor necrosis factor-alpha converting enzyme increases the malignant potential in human pancreatic ductal adenocarcinoma.

A disintegrin and metalloproteinase (ADAM) molecules are known for their unique potential to combine adhesion, proteolysis, and signaling. To understand the role of ADAM17/tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in pancreatic ductal adenocarcinoma (PDAC), we investigated its expression, function, and in vitro regulation. ADAM17/TACE mRNA was expressed in 3 of 10 normal pancreatic tissues, 6 of 8 samples from patients with chronic pancreatitis, 10 of 10 PDAC tissues, and 9 of 9 pancreatic cancer cell lines, but it was absent in primary duct epithelial cells.

Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations.

Several diverse genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These mouse models have a spectrum of pathologic changes; however, until now, there has been no uniform nomenclature to characterize these changes. An international workshop, sponsored by The National Cancer Institute and the University of Pennsylvania, was held from December 1 to 3, 2004 with the goal of establishing an internationally accepted uniform nomenclature for the pathology of genetically engineered mouse models of pancreatic exocrine neoplasia.

Histopathological diagnosis of pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms: interobserver agreement.

Objectives: The goal of this study was to evaluate the consistency of distinction between pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary-mucinous neoplasms (IPMN) and the hypothesis that guidelines for their distinction might be inadequate.

Methods: A group of 93 pancreas specimens from surgical resections or autopsies that contained lesions consistent with histopathological diagnoses of PanIN-1A, PanIN-1B, PanIN-2, or IPMN (adenoma or borderline) was collected. The classification of these neoplasms by 6 pathologists, 2 from Europe, 2 from Japan, and 2 from the United States, was compared.

Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions.

Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed.

Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study.

Now that more than two decades have passed since the first reports of intraductal papillary-mucinous neoplasms (IPMNs), it has become clear that IPMN consists of a spectrum of neoplasms with both morphological and immunohistochemical variations. At a meeting of international experts on pancreatic precursor lesions held in 2003, it was agreed that a consensus classification of IPMN subtypes should be established to enable a more detailed analysis of the clinicopathological significance of the variations. Based on our experience and on information from the literature, we selected representative histological examples of IPMNs and defined a consensus nomenclature and criteria for classifying variants as distinctive IPMN subtypes including gastric type, intestinal type, pancreatobiliary type, and oncocytic type.

Application of fluorescence difference gel electrophoresis saturation labelling for the analysis of microdissected precursor lesions of pancreatic ductal adenocarcinoma.

In order to identify new molecular markers for pancreatic intra-epithelial neoplasias (PanINs), the precursor lesions of pancreatic ductal adenocarcinoma, we established a proteomics approach analysing microdissected PanIN cells. Due to the limited amount of proteins available from microdissection, we developed a procedure including fluorescence dye saturation labelling in combination with high resolution two-dimensional gel electrophoresis. With this procedure we were able to analyse proteins extracted from 1000 microdissected cells with a high resolution of up to 2500 protein spots.

Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes.

Pancreatic ductal adenocarcinoma is the eighth most common cancer with the lowest overall 5-year relative survival rate of any tumor type today. Expression profiling using microarrays has been widely used to identify genes associated with pancreatic cancer development. To extract maximum value from the available gene expression data, we applied a meta-analysis to search for commonly differentially expressed genes in pancreatic ductal adenocarcinoma.

High nuclear S100A6 (Calcyclin) is significantly associated with poor survival in pancreatic cancer patients.

Recent studies have reported elevated levels of S100A6 in pancreatic ductal adenocarcinoma cells. Here, we describe a detailed analysis of S100A6 expression in benign (n = 32), malignant (n = 60), and premalignant pancreatic ductal cells [96 pancreatic intraepithelial neoplasias (PanIN) from 46 patients]. S100A6 staining was more intense in malignant cells than in benign cells (P = 0.

Precursor lesions of invasive breast cancer.

The increasing application of mammography, mainly in screening programs for the early detection of breast cancer, and the high technical standard of imaging has resulted in the detection of clinically occult breast tumors. Considering that only diagnosis at an early stage will be able to change the prognosis of breast cancer, this diagnostic challenge appears to be the most exciting field in both breast imaging and breast pathology. Especially the precursor lesions need to be diagnosed and defined precisely to understand their prognostic significance.

Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis.

Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed.

Autoimmune pancreatitis: pathological findings.

In recent years, autoimmune pancreatitis has been established as a special type of chronic pancreatitis. It is characterized by its histopathological and immunological features. The morphological hallmarks are periductal infiltration by lymphocytes and plasma cells and granulocytic epithelial lesions with consequent destruction of the duct epithelium and venulitis.

Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.

S100P is a member of the S100 family of calcium-binding proteins and there have been several recent reports of its overexpression in pancreatic ductal adenocarcinoma (PDAC). We have used Far Western screening and in vitro interaction assays to identify and confirm a novel target protein for S100P. We have named this protein S100PBPR, and shown that its interaction with S100P is dependent on Ca(2+) or Mg(2+).

Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential.

Profiles of gene transcription have begun to delineate the molecular basis of ovarian cancer, including distinctions between carcinomas of differing histology, tumor progression and patient outcome. However, the similarities and differences among the most commonly diagnosed noninvasive borderline (low malignant potential, LMP) lesions and invasive serous carcinomas of varying grade (G1, G2 and G3) have not yet been explored. Here, we used oligonucleotide arrays to profile the expression of 12,500 genes in a series of 57 predominantly stage III serous ovarian adenocarcinomas from 52 patients, eight with borderline tumors and 44 with adenocarcinomas of varying grade.

Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy-related death and is the eighth most common cancer with the lowest overall 5-year relative survival rate. To identify new molecular markers and candidates for new therapeutic regimens, we investigated the gene expression profile of microdissected cells from 11 normal pancreatic ducts, 14 samples of PDAC, and 4 well-characterized pancreatic cancer cell lines using the Affymetrix U133 GeneChip set. RNA was extracted from microdissected samples and cell lines, amplified, and labeled using a repetitive in vitro transcription protocol.

Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens.

Background And Aims: Autoimmune pancreatitis seems to be a disease with a heterogeneous appearance. Our intention was to establish key diagnostic criteria, define grades of severity and activity, identify features of potential subtypes and evaluate the diagnostic relevance of biopsy specimens.

Methods: Histopathological criteria and clinical features were recorded in pancreatic resection specimens from 53 patients who were found to have chronic pancreatitis lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or duodenal wall inflammation.

aRNA-longSAGE: a new approach to generate SAGE libraries from microdissected cells.

Large-scale gene expression analyses of microdissected primary tissue are still difficult because generally only a limited amount of mRNA can be obtained from microdissected cells. The introduction of the T7-based RNA amplification technique was an important step to reduce the amount of RNA needed for such analyses. This amplification technique produces amplified antisense RNA (aRNA), which so far has precluded its direct use for serial analysis of gene expression (SAGE) library production.

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms.

Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms.

The pathology of ductal-type pancreatic carcinomas and pancreatic intraepithelial neoplasia: insights for clinicians.

The phenotypic classification of pancreatic neoplasms is based on their cellular lineage. Thus, tumors with a ductal, acinar, and endocrine phenotype can be distinguished. Most pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas.

Where and when does pancreatic carcinoma start?

The phenotypic classification of pancreatic neoplasms is based on their cellular lineage. Thus, tumors with a ductal, acinar and endocrine phenotype can be distinguished. Most pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas.