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Ductal Adenocarcinoma (ductal + adenocarcinoma)
Kinds of Ductal Adenocarcinoma Selected AbstractsDuctal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical managementBJU INTERNATIONAL, Issue 4 2010Hakan Aydin Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA). PATIENTS AND METHODS The presence of DCP in transrectal ultrasonography-guided prostate biopsy (TRUSB) is associated with adverse pathological findings at radical prostatectomy (RP) and clinical outcomes, and the significance of detecting DCP initially in transurethral biopsy (UB) or transurethral resection (TURP) in the present era of screening with prostate-specific antigen (PSA) is unclear. The study included 23 cases of pure DCP without acinar PA diagnosed on UB or TURP. Demographic information, serum PSA level, follow-up surgical procedures (RP, TURP or TRUSB) and outcome data were collected. RESULTS The mean age of the men was 67.5 years and the mean PSA level before the procedure was 12.5 ng/mL; 14 cases were detected on UB and nine were diagnosed on TURP. The mean (range) follow-up was 4 (1,23) months after the initial procedure. In all, 21 (89%) patients had DCP or PA in follow-up procedures. Two (11%) patients had no residual cancer, one on RP and the other on two repeat TURPs. DCP or PA was found in 12 RP cases; four patients had Gleason score 7 PA, three of which were organ-confined, and eight had Gleason score ,8 PA. Extraprostatic extension, seminal vesicle invasion and regional lymph node metastasis were present in seven, six and two cases, respectively. CONCLUSIONS Most DCP diagnosed on UB or TURP in this contemporary series was associated with aggressive PA, but a subset presented as a small periurethral tumour with no concomitant acinar PA, and was eradicated by the initial biopsy/TURP alone. We recommend that patients with a diagnosis of DCP on UB or TURP undergo follow-up TURP and TRUSB before radical surgery is offered. [source] Endoscopic ultrasound-guided fine-needle aspiration of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: A report of 2 cases with literature reviewDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2007Shefali Chopra M.D. Abstract Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is rare. Histologically it mimics the giant cell tumor of the bone and may be associated with a ductal adenocarcinoma. We recently encountered two such cases, both of which were biopsied by EUS-guided FNA. Abundant multinucleated osteoclast-like giant cells and many uniform mononuclear cells were present in case 1 so that the diagnosis was made. In case 2, many mononuclear tumor cells with vacuolated and basophilic cytoplasm were present, and rare osteoclast-like giant cells were seen. A diagnosis of adenocarcinoma was made. In both cases, no conspicuous nuclear pleomorphism was noted in the mononuclear cells or the multinucleated giant cells. The histology of case 2 revealed a pure undifferentiated carcinoma with osteoclast-like giant cells. In addition, a liver biopsy revealed globular amyloidosis. To our knowledge, this is the first report of pancreatic undifferentiated carcinoma with osteoclast-like giant cells sampled by EUS-guided FNA and the first case of hepatic globular amyloidosis associated with this tumor. Diagn. Cytopathol. 2007;35:601-606. © 2007 Wiley-Liss, Inc. [source] Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreasGENES TO CELLS, Issue 7 2008Tetsu 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] Decreased expression and promoter methylation of the menin tumor suppressor in pancreatic ductal adenocarcinomaGENES, CHROMOSOMES AND CANCER, Issue 5 2009Ilaria Cavallari Loss of menin, a tumor suppressor coded by the MEN1 gene, is a key factor in the pathogenesis of multiple endocrine neoplasia type I and in a percentage of sporadic endocrine tumors of the pancreas and parathyroid glands. This study investigated expression of the menin protein in the normal exocrine pancreas and in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic tumor. Immunofluorescence (IF) analyses showed that menin is expressed at high levels in normal acinar and duct cells. Examination of 24 clinical samples of PDAC revealed a pronounced decrease in menin expression in all tumors examined. To identify alterations underlying this defect, we searched for disruption and epigenetic silencing of the MEN1 gene. Analysis of nine laser-microdissected tumors revealed loss of heterozygosity of intragenic (one tumor) or adjacent (three tumors) MEN1 microsatellite markers. Methylation of CpG sites in the MEN1 promoter was documented in five of 24 tumors. IF analyses also revealed low to undetectable menin expression in the PDAC cell lines MiaPaCa-2 and Panc-1. Ectopic expression of menin in these cells resulted in a marked alteration of the cell cycle, with an increase in the G1/S+G2 ratio. These findings represent the first evidence that the MEN1 gene is a target of mutation and methylation in PDAC and that menin influences the cell cycle profile of duct cells. © 2009 Wiley-Liss,Inc. [source] Preoperative staging and evaluation of resectability in pancreatic ductal adenocarcinomaHPB, Issue 1 2004R Andersson Background Cancer of the pancreas is a common disease, but the large majority of patients have tumours that are irresectable at the time of diagnosis. Moreover, patients whose tumours are clearly beyond surgical cure are best treated non-operatively, if possible, by relief of biliary obstruction and percutaneous biopsy to confirm the diagnosis and then consideration of oncological treatment, notably chemotherapy. These facts underline the importance of a standard protocol for the preoperative determination of operability (is it worth operating?) and resectability (is there a chance that the tumour can be removed?). Recent years have seen the advent of many new techniques, both radiological and endoscopic, for the diagnosis and staging of pancreatic cancer. It would be impracticable in time and cost to submit every patient to every test. This review will evaluate the available techniques and offer a possible algorithm for use in routine clinical practice. Discussion In deciding whether to operate with a view to resecting a pancreatic cancer, the surgeon must take into account factors related to the patient, the tumour and the institution and team entrusted with the patient's care. Patient-related factors include age, general health, pain and the presence or absence of malnutrition and an acute phase inflammatory response. Tumour-related factors include tumour size and evidence of spread, whether to adjacent organs (notably major blood vessels) or further afield. Hospital-related factors chiefly concern the volume of pancreatic cancer treated and thus the experience of the whole team. Determination of resectability is heavily dependent upon detailed imaging. Nowadays conventional ultrasonography can be supplemented by endoscopic, laparoscopic and intra-operative techniques. Computed tomography (CT) remains the single most useful staging modality, but MRI continues to improve. PET scanning may demonstrate unsuspected metastases and likewise laparoscopy. Diagnostic cholangiography can be performed more easily by MR techniques than by endoscopy, but ERCP is still valuable for preoperative biliary decompression in appropriate patients. The role of angiography has declined. Percutaneous biopsy and peritoneal cytology are not usually required in patients with an apparently resectable tumour. The prognostic value of tumour marker levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy or chemoradiation may have a role in down-staging an irresectable tumour sufficiently to render it resectable. Selective use of diagnostic laparoscopy staging is potentially helpful in determination of resectability. Laparotomy remains the definitive method for determining the resectability of pancreatic cancer, with or without portal vein resection, and should be undertaken in suitable patients without clear-cut evidence of irresectability. [source] In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2006Daisuke Ito Abstract Mammalian target of rapamycin (mTOR) is considered to be a major effector of cell growth and proliferation that controls protein synthesis through a large number of downstream targets. We investigated the expression of the phosphatidylinositol 3,-kinase (PI3K)/mTOR signaling pathway in human pancreatic cancer cells and tissues, and the in vivo antitumor effects of the mTOR inhibitor CCI-779 with/without gemcitabine in xenograft models of human pancreatic cancer. We found that the Akt, mTOR and p70 S6 kinase (S6K1) from the PI3K/mTOR signaling pathway were activated in all of the pancreatic cancer cell lines examined. When surgically resected tissue specimens of pancreatic ductal adenocarcinoma were examined, phosphorylation of Akt, mTOR and S6K1 was detected in 50, 55 and 65% of the specimens, respectively. Although CCI-779 had no additive or synergistic antiproliferative effect when combined with gemcitabine in vitro, it showed significant antitumor activity in the AsPC-1 subcutaneous xenograft model as both a single agent and in combination with gemictabine. Furthermore, in the Suit-2 peritoneal dissemination xenograft model, the combination of these 2 drugs achieved significantly better survival when compared with CCI-779 or gemcitabine alone. These results demonstrate promising activity of the mTOR inhibitor CCI-779 against human pancreatic cancer, and suggest that the inhibition of mTOR signaling can be exploited as a potentially tumor-selective therapeutic strategy. © 2005 Wiley-Liss, Inc. [source] ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancerJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2007N. Valkovskaya Abstract ADAM8 belongs to a family of transmembrane proteins implicated in cell,cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy. [source] Magnetic resonance imaging in the detection of pancreatic neoplasmsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2007Liang ZHONG Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins. [source] Pancreatic adenocarcinoma in a young patient population,12-year experience at Memorial Sloan Kettering Cancer CenterJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2009A. Duffy MD Abstract Background There is a dearth of data in a younger population of patients with pancreatic ductal adenocarcinoma (PAC) regarding epidemiology, genetics, prognosis, and outcome. This report examines a large cohort of patients with PAC ,45 years of age evaluated at MSKCC over a 12-year period. Methods A retrospective analysis of patients referred to MSKCC with PAC identified from the institutional tumor registry, who were ,45 years on the date of the diagnostic biopsy, between January 1995 and February 2008, was performed. Information reviewed included demographics, clinical and pathological staging, surgical management, therapy, date of relapse, death or last follow-up. Survival curves were estimated using the Kaplan,Meier method and compared using the log-rank test. Results One hundred thirty-six cases of PAC, age ,45 years at diagnosis, were identified. Seventy-four (54%) females, 62 (46%) males. Age range: 24,45; 4, 38, and 94 patients in age groups 20,29, 30,39, 40,45 years, respectively. Fifty (37%) had a smoking history. Fourteen (10.3%) had a positive family history of PAC. Thirty-five (25.7%) underwent a curative resection for localized disease. Twenty-eight (20.1%) presented with locally advanced, inoperable disease. Sixty-eight (50%) presented as AJCC Stage IV. Twenty-three (37%) of those resected underwent adjuvant chemoradiation. Thirteen received adjuvant gemcitabine. The median overall survival for the entire cohort was 12.3 months (95% CI 10.2,14.0 months). The median overall survival for the patients with locally resectable disease was 41.8 months (95% CI 20.3,47 months). The median overall survival for the patients who presented with locally advanced, unresectable disease was 15.3 months (95% CI 12,19.3 months). The median overall survival for those who presented with metastatic disease was 7.2 months (95% CI 5.2,9.5 months). Conclusions This is the largest reported cohort of young patients with PAC ,45 years of age. The data suggest that patients with stages I,II disease may have an improved prognosis, however the prognosis for stages III,IV patients appears to be similar to the typical (older) patient population with PAC. J. Surg. Oncol. 2009;100:8,12. © 2009 Wiley-Liss, Inc. [source] Invasive intraductal papillary-mucinous neoplasm of the pancreas: Comparison with pancreatic ductal adenocarcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2009Yoshiaki Murakami MD Abstract Background and Objectives The aim of this study was to clarify the clinicopathological differences between patients with invasive intraductal papillary-mucinous neoplasm (IPMN) of the pancreas and pancreatic ductal adenocarcinoma. Methods The medical records of 16 patients with invasive IPMN and 106 patients with pancreatic ductal adenocarcinoma, who underwent surgical resection, were retrospectively reviewed, and the clinicopathological factors and survival were compared between the two groups. Results The presence of retroperitoneal tissue invasion, portal or splenic vein invasion, nodal involvement, and positive surgical margins were significantly lower in patients with invasive IPMN than in those with ductal adenocarcinoma (P,<,0.05). The actuarial 5-year overall survival rates in patients with invasive IPMN and ductal carcinoma were 40% and 18%, respectively (P,=,0.008). However, the actuarial 5-year survival rate of patients with invasive IPMN was only 27% for UICC stage II disease, although this was significantly higher than that of patients with UICC stage II ductal adenocarcinoma (P,=,0.049). Conclusions Invasive IPMN has a favorable prognosis compared with pancreatic ductal adenocarcinoma that is likely due to the less aggressive nature of the disease. However, the prognosis for cases of advanced invasive IPMN is not always favorable despite complete tumor resection. J. Surg. Oncol. 2009;100:13,18. © 2009 Wiley-Liss, Inc. [source] The case for routine use of adjuvant therapy in pancreatic cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 7 2007Eugene P. Kennedy MD Abstract Pancreatic cancer is a devastating disease with a poor prognosis for most patients. Surgical resection remains the cornerstone of treatment, providing the only realistic hope of long-term survival. Even with optimal surgical management, 5-year survival averages 15% to 20% for resectable disease. Progress is being made, however. Currently, the benefits of postoperative therapy for resected pancreatic ductal adenocarcinoma appear clear, and recommendations for such therapy appear to us to be well justified. Additional benefit to patients awaits the development of new agents, molecular targeted drugs, and novel approaches such as immunotherapy. J. Surg. Oncol. 2007;95:597,603. © 2007 Wiley-Liss, Inc. [source] Meta-analysis: the use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk for different exposure categoriesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2007G. CAPURSO Summary Background, A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear. Aim, To conduct a systematic review and meta-analysis on the relation between ASA/NSAIDs exposure and the risk of PDAC. Methods, We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case-control) studies and randomized controlled trials examining exposure to ASA and/or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose. Results, Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971,2004; all but one study took place in the US. The pooled OR were 0.99 (0.83,1.19), 1.11 (0.84,1.47) and 1.09 (0.67,1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I2 ranging 60,86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information. Conclusions, This study did not show an association between ASA/NSAIDs and PDAC. The large baseline exposure in controls in North-America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue. [source] Differential expression of insulin-like growth factor binding protein-5 in pancreatic adenocarcinomas: Identification using DNA microarrayMOLECULAR CARCINOGENESIS, Issue 11 2006Sarah K. Johnson Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressiveness and resistance to both radiation and chemotherapeutic treatment. To better understand the molecular pathogenesis of pancreatic cancer, DNA array technology was employed to identify genes differentially expressed in pancreatic tumors when compared to non-malignant pancreatic tissues. RNA isolated from 11 PDACs and 14 non-malignant bulk pancreatic duct specimens was used to probe Affymetrix U95A DNA arrays. Genes that displayed at least a fourfold differential expression were identified and real-time quantitative PCR was used to verify the differential expression of selected upregulated genes. Interrogation of the DNA array revealed that 73 genes were upregulated in PDACs and 77 genes were downregulated. The majority of the 150 genes identified have not been previously reported to be differentially expressed in pancreatic tumors, although a number of the upregulated transcripts have been reported previously. Immunohistochemistry was used to correlate calponin and insulin-like growth factor binding protein-5 (IGFBP-5) RNA levels with protein expression in PDACs and revealed peritumoral calponin staining in the reactive stroma and intense focal staining of islets cells expressing IGFBP-5 at the edge of tumors; thus implicating the interplay of various cell types to promote neoplastic cell growth within pancreatic carcinomas. As a potential modulator of cell proliferation, the overexpression of IGFBP-5 may, therefore, play a significant role in the malignant transformation of normal pancreatic epithelial cells. © 2006 Wiley-Liss, Inc. [source] CD97, CD95 and Fas-L clearly discriminate between chronic pancreatitis and pancreatic ductal adenocarcinoma in perioperative evaluation of cryocut sectionsPATHOLOGY INTERNATIONAL, Issue 2 2002Carsten Boltze It is a major problem to distinguish between pancreatitis and pancreatic adenocarcinoma when it comes to the perioperative evaluation of pancreatic cryocut sections. In this respect, pathologists are showing a steadily growing interest in the potential application of apoptotic and dedifferentiation factors as diagnostic and prognostic markers. This study investigated the mRNA and protein expression of CD97, CD95 and Fas-L in snap-frozen material obtained from human pancreatic ductal adenocarcinomas (PDC; n = 50), tissues from pancreatitis (PT; n = 40) and normal pancreatic tissues (PN; n = 36). Reverse transcription,polymerase chain reaction (RT,PCR) analysis revealed that CD97, CD95 and Fas-L mRNA were expressed on a similarly high level in all tissues. In contrast, short time immunohistochemical evaluation showed that the CD95 protein was strongly expressed in PT and PN, but not in PDC. Fas-L protein was expressed strongly in PDC, whereas only weak or no expression was noted in PT or PN. CD97 protein expression was detected only in PT and in poorly differentiated PDC. Our data demonstrate that CD97, CD95 and Fas-L can be used as additional markers to distinguish between pancreatitis and pancreatic duct cell carcinoma in cryocut sections. [source] Adenoviral-mediated gene transfer of Gadd45a results in suppression by inducing apoptosis and cell cycle arrest in pancreatic cancer cellTHE JOURNAL OF GENE MEDICINE, Issue 1 2009Yunfeng Li Abstract Background The extremely poor prognosis of patients with pancreatic ductal adenocarcinoma indicates the need for novel therapeutic approaches. The growth arrest and DNA damage-inducible (Gadd) gene Gadd45a is a member of a group of genes that are induced by DNA damaging agents and growth arrest signals. Methods We evaluated the biological activity of Gadd45a in pancreatic ductal adenocarcinoma cancer-derived cell lines and assessed the efficacy of a combined treatment with adenoviral-mediated expression of Gadd45a (Ad-G45a) and anticancer drug (Etoposide, cisplatin, 5-fluorouracil, respectively) for the PANC1 cell line. Results Gadd45a is variously expressed in cell lines derived from pancreatic ductal adenocarcinoma cancer and adenoviral-mediated expression of Gadd45a (Ad-G45a) in these cells results in apoptosis via caspase activation and cell-cycle arrest in the G2/M phase. Gadd45a significantly increased the chemosensitivity of PANC1, which may be due to abundant apoptosis induction and cell cycle arrest. By combinational treatment of Ad-G45a infection and chemotherapeutics, Gadd45a expression was elevated to a higher extent in cancer cells with wild-type p53 than in that with knocked-out p53 status, indicating a higher chemosensitivity to cancer chemotherapy. Conclusions Gadd45a may be a promising candidate for use in cancer gene therapy in combination with chemotherapeutic agents. Copyright © 2008 John Wiley & Sons, Ltd. [source] Ductal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical managementBJU INTERNATIONAL, Issue 4 2010Hakan Aydin Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA). PATIENTS AND METHODS The presence of DCP in transrectal ultrasonography-guided prostate biopsy (TRUSB) is associated with adverse pathological findings at radical prostatectomy (RP) and clinical outcomes, and the significance of detecting DCP initially in transurethral biopsy (UB) or transurethral resection (TURP) in the present era of screening with prostate-specific antigen (PSA) is unclear. The study included 23 cases of pure DCP without acinar PA diagnosed on UB or TURP. Demographic information, serum PSA level, follow-up surgical procedures (RP, TURP or TRUSB) and outcome data were collected. RESULTS The mean age of the men was 67.5 years and the mean PSA level before the procedure was 12.5 ng/mL; 14 cases were detected on UB and nine were diagnosed on TURP. The mean (range) follow-up was 4 (1,23) months after the initial procedure. In all, 21 (89%) patients had DCP or PA in follow-up procedures. Two (11%) patients had no residual cancer, one on RP and the other on two repeat TURPs. DCP or PA was found in 12 RP cases; four patients had Gleason score 7 PA, three of which were organ-confined, and eight had Gleason score ,8 PA. Extraprostatic extension, seminal vesicle invasion and regional lymph node metastasis were present in seven, six and two cases, respectively. CONCLUSIONS Most DCP diagnosed on UB or TURP in this contemporary series was associated with aggressive PA, but a subset presented as a small periurethral tumour with no concomitant acinar PA, and was eradicated by the initial biopsy/TURP alone. We recommend that patients with a diagnosis of DCP on UB or TURP undergo follow-up TURP and TRUSB before radical surgery is offered. [source] Prostate carcinoma with testicular or penile metastasesCANCER, Issue 10 2002Clinical, immunohistochemical features, pathologic Abstract BACKGROUND Despite the proximity, prostate carcinoma seldom metastasizes to the penis or testis. METHODS In the current study, the authors retrospectively examined the clinical history of 12 patients with prostate carcinoma and testicular or penile metastases. Pathologic review and immunohistochemical staining were performed on tumors from eight of these patients. RESULTS Patients with prostate carcinoma and testicular or penile metastasis responded to androgen ablative therapy (median duration, 33 months). They were predisposed to developing persistent or recurrent urinary symptoms and visceral metastases. Six of 9 evaluable patients had elevated serum carcinoembryonic antigen levels (> 6 ng/mL), whereas 2 of 10 patients had low or undetectable serum prostate specific antigen levels (< 4 ng/mL). In seven of the eight patients for whom specimens were available, the tumors were found to contain histologic features that were compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate. CONCLUSIONS Patients with prostate carcinoma and testicular or penile metastases have unique clinical and pathologic characteristics. Many of these patients' tumors are compatible with a subtype of prostate carcinoma known as ductal adenocarcinoma. Further studies need to be performed to elucidate the biologic basis of the various histologic subtypes of prostate carcinoma. Cancer 2002;94:2610,7. © 2002 American Cancer Society. DOI 10.1002/cncr.10546 [source] Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profilingCANCER SCIENCE, Issue 1 2010Seiko Hirono Lymph node metastasis (LNM) is the most important prognostic factor in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). In this study, we aimed to identify molecular markers associated with LNM in PDAC using genome-wide expression profiling. In this study, laser microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between PDAC cells with and without LNM obtained from 20 patients with PDAC. Immunohistochemical staining was used to confirm the clinical significance of these markers in an additional validation set of 43 patients. In the results, microarray profiling identified 46 genes that were differently expressed between PDAC with and without LNM with certain significance. Four of these biomarkers were validated by immunohistochemical staining for association with LNM in PDAC in an additional validation set of patients. In 63 patients with PDAC, significant LNM predictors in PDAC elucidated from multivariate analysis were low expression of activating enhancer binding protein 2 (AP2,) (P = 0.012) and high expression of mucin 17 (MUC17) (P = 0.0192). Furthermore, multivariate analysis revealed that AP2, -low expression and MUC17 -high expression are independent prognostic factors for poor overall survival (P = 0.0012, 0.0001, respectively). In conclusion, AP2, and MUC17 were independent markers associated with LNM of PDAC. These two markers were also associated with survival in patients with resected PDAC. We demonstrate that AP2, and MUC17 may serve as potential prognostic molecular markers for LNM in patients with PDAC. (Cancer Sci 2009) [source] Tumor,stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cellsCANCER SCIENCE, Issue 12 2009Hayato Fujita Pancreatic ductal adenocarcinoma is often characterized by an abundant desmoplastic stroma that is partially induced by activated pancreatic stellate cells (PSCs). Indirect co-culture has often been used to investigate the effects of cancer,stromal interactions on the proliferation of cancer cells, but the effects of cell,cell adhesion and juxtacrine signaling between cancer and stromal cells cannot be evaluated using this method. This study aimed to establish a simplified direct co-culture system that could be used to quantify populations of cancer cells in co-culture with PSCs, and to evaluate the effects of direct cell contact on the proliferation of cancer cells. We established three green fluorescent protein (GFP)-expressing pancreatic cancer cell lines and were able to quantify them with high reliability and reproducibility, even when co-cultured directly with PSCs, using a color plate reader. We assessed the differential effects of direct and indirect co-culture with PSCs on the proliferation of cancer cells, and found that the proliferation of GFP-expressing pancreatic cancer cell lines was dramatically enhanced by direct co-culture with PSCs, compared with the indirect co-culture system. We also found that direct co-culture of cancer cells and PSCs activated the Notch signaling pathway in both cell types. Direct cell contact between cancer cells and PSCs plays an important role in the control of cancer cell proliferation, and is essential to the understanding of tumor,stromal interactions. (Cancer Sci 2009; 100: 2309,2317) [source] Over-expression of cysteine proteinase inhibitor cystatin 6 promotes pancreatic cancer growthCANCER SCIENCE, Issue 8 2008Masayo Hosokawa Pancreatic ductal adenocarcinoma (PDAC) shows the worst mortality among the common malignancies and development of novel therapies for PDAC through identification of good molecular targets is an urgent issue. Among dozens of over-expressing genes identified through our gene-expression profile analysis of PDAC cells, we here report CST6 (Cystatin 6 or E/M) as a candidate of molecular targets for PDAC treatment. Reverse transcriptase,polymerase chain reaction (RT-PCR) and immunohistochemical analysis confirmed over-expression of CST6 in PDAC cells, but no or limited expression of CST6 was observed in normal pancreas and other vital organs. Knock-down of endogenous CST6 expression by small interfering RNA attenuated PDAC cell growth, suggesting its essential role in maintaining viability of PDAC cells. Concordantly, constitutive expression of CST6 in CST6-null cells promoted their growth in vitro and in vivo. Furthermore, the addition of mature recombinant CST6 in culture medium also promoted cell proliferation in a dose-dependent manner, whereas recombinant CST6 lacking its proteinase-inhibitor domain and its non-glycosylated form did not. Over-expression of CST6 inhibited the intracellular activity of cathepsin B, which is one of the putative substrates of CST6 proteinase inhibitor and can intracellularly function as a pro-apoptotic factor. These findings imply that CST6 is likely to involve in the proliferation and survival of pancreatic cancer probably through its proteinase inhibitory activity, and it is a promising molecular target for development of new therapeutic strategies for PDAC. (Cancer Sci 2008; 99: 1626,1632) [source] Novel tumor marker REG4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting REG4CANCER SCIENCE, Issue 11 2006Akio Takehara Pancreatic ductal adenocarcinoma (PDAC) shows the worst mortality rate among common malignancies, with a 5-year survival rate of only 4%, and the majority of PDAC patients are diagnosed at an advanced stage in which no effective therapy is available at present. Although the proportion of curable cases is still not so high, surgical resection of early stage PDAC is the only way to cure the disease. Hence, establishment of a screening strategy to detect early stage PDAC by novel serological markers is required urgently, and development of novel molecular therapies for PDAC treatment is also eagerly expected. We here report overexpression of REG4, a new member of the regenerating islet-derived (REG) family, in PDAC cells on the basis of genome-wide cDNA microarray analysis as well as reverse transcription,polymerase chain reaction and immunohistochemical analysis. We also detected significant elevation of REG4 in the serum of some patients with early-stage PDAC using our enzyme-linked immunosorbent assay system, indicating the possibility of REG4 as a new serological marker of PDAC. Furthermore, we found that knockdown of endogenous REG4 expression in PDAC cell lines with small interfering RNA caused a decrease in cell viability. Concordantly, addition of recombinant REG4 to the culture medium enhanced growth of a PDAC cell line in a dose-dependent manner. A monoclonal antibody against REG4 neutralized its growth-promoting effects and attenuated significantly the growth of PDAC cells. These findings indicate that REG4 is a promising tumor marker to screen early-stage PDAC, and also that neutralization of REG4 by the antibody may offer novel potential tools for the treatment of PDAC. (Cancer Sci 2006; 97: 1191,1197) [source] Molecular mechanisms of pancreatic carcinogenesisCANCER SCIENCE, Issue 1 2006Toru 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] Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinomaCANCER SCIENCE, Issue 7 2004Yusuke Oji The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 anti-sense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product. [source] Expression of oncogenic K-ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cellsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Shujie Zhao Abstract Activating mutation of K-ras and inactivation of DPC4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). A separate common event in PDAC progression is increased expression of phosphotyrosine kinase receptors (PTKRs). In our study, we examined whether activating mutations of K-ras and loss of Smad4 play a role in causing the aberrant expression of PTKRs. Immortalized human pancreas ductal cells (HPNE) were genetically modified by expressing oncogenic K-ras and/or by shRNA knockdown of Smad4. EGFR and erbB2 protein levels but not Ron or IGF-1R were substantially upregulated in HPNE cells that express K-ras(GD12). The increased expression of EGFR in HPNE cells that expressed K-ras(GD12) was mediated by both stabilizing EGFR protein and by increasing EGFR transcription. TGF-, signaling partially suppressed K-ras(GD12) induced EGFR transcription in Smad4 intact HPNE cells; whereas knockdown of Smad4 in cells expressing K-ras(GD12) further enhanced expression of EGFR and erbB2. The upregulation of EGFR and erbB2 was associated with an increase of invasion, which was blocked by a kinase inhibitor of EGFR. Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion. [source] Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growthINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Nobuyasu Takahashi Abstract The protein products of the Dickkopf (DKK) genes are antagonists of Wnt glycoproteins, which participate in tumor development and progression by binding to frizzled receptors. In this study, the expression of DKK-1 was analyzed in a panel of 43 human cultured carcinoma cell lines. DKK-1 expression was consistently and significantly upregulated in pancreatic carcinoma cell lines. Low level of DKK-3 expression was also seen. In contrast, the expression of DKK-2 and -4 was not detectable in most pancreatic carcinoma cell lines. The overexpression of DKK-1 was confirmed in surgically resected human pancreatic cancer tissues, in which the mRNA level was evaluated in paired samples from cancerous and noncancerous pancreatic tissues. In ductal adenocarcinomas (23 cases), DKK-1 mRNA levels were significantly upregulated compared to corresponding noncancerous tissues in a statistically significant level. To test the biological role of DKK-1 in pancreatic carcinoma cells, we performed a knockdown of DKK-1 in SUIT-2 human pancreatic adenocarcinoma cell line and S2-CP8, its metastatic subline, using a retroviral short hairpin RNA expression vector. DKK-1 knockdown resulted in reduced migratory activity of SUIT-2 in vitro. The in vitro growth rate and Matrigel invasion were also suppressed by DKK-1 knockdown in S2-CP8 cells. Collectively, the evidence suggests that, despite of its presumed antagonistic role in Wnt signaling, DKK-1 may have a role in the aggressiveness of pancreatic carcinoma cells and could, therefore, serve as a novel biomarker of pancreatic cancer. [source] Magnetic resonance imaging in the detection of pancreatic neoplasmsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2007Liang ZHONG Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins. [source] CD97, CD95 and Fas-L clearly discriminate between chronic pancreatitis and pancreatic ductal adenocarcinoma in perioperative evaluation of cryocut sectionsPATHOLOGY INTERNATIONAL, Issue 2 2002Carsten Boltze It is a major problem to distinguish between pancreatitis and pancreatic adenocarcinoma when it comes to the perioperative evaluation of pancreatic cryocut sections. In this respect, pathologists are showing a steadily growing interest in the potential application of apoptotic and dedifferentiation factors as diagnostic and prognostic markers. This study investigated the mRNA and protein expression of CD97, CD95 and Fas-L in snap-frozen material obtained from human pancreatic ductal adenocarcinomas (PDC; n = 50), tissues from pancreatitis (PT; n = 40) and normal pancreatic tissues (PN; n = 36). Reverse transcription,polymerase chain reaction (RT,PCR) analysis revealed that CD97, CD95 and Fas-L mRNA were expressed on a similarly high level in all tissues. In contrast, short time immunohistochemical evaluation showed that the CD95 protein was strongly expressed in PT and PN, but not in PDC. Fas-L protein was expressed strongly in PDC, whereas only weak or no expression was noted in PT or PN. CD97 protein expression was detected only in PT and in poorly differentiated PDC. Our data demonstrate that CD97, CD95 and Fas-L can be used as additional markers to distinguish between pancreatitis and pancreatic duct cell carcinoma in cryocut sections. [source] Molecular mechanisms of pancreatic carcinogenesisCANCER SCIENCE, Issue 1 2006Toru 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] Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinomaCANCER SCIENCE, Issue 7 2004Yusuke Oji The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 anti-sense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product. [source] | ||||||||||||||||||||||||||||