(1/113) De novo expression of CD44 in prostate carcinoma is correlated with systemic dissemination of prostate cancer.

AIMS: To evaluate the role of CD44 in early steps in the development of prostate cancer, and to assess the biological significance of preneoplastic lesions in prostate cancer. METHODS: 38 patients with clinically localised prostate cancer were studied. The standard form of CD44 (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin embedded tumour tissue by immunohistochemistry. Disseminated prostatic cells were detected by prostate specific membrane antigen reverse transcriptase polymerase chain reaction in the blood of each patient before radical prostatectomy. RESULTS: In normal or benign prostate glands, only basal cells showed CD44H and v6 labelling. Fourteen of the 38 prostate cancers (37%) had CD44H membranous staining of prostatic tumour cells. In 18 patients (47%), circulating prostatic cells were detected in blood before surgery. Although no correlation between the expression of CD44 and the Gleason score or staging was observed, a significant correlation was found between the expression of CD44H by tumour cells and prostatic cell blood dissemination (p = 0.04). In 28 cases, foci of prostatic intraepithelial neoplasia were observed, and nine had CD44H immunostaining. CONCLUSIONS: De novo expression of CD44 by prostatic tumour cells is associated with systemic dissemination of prostate cells independently of pathological criteria.  (+info)

(2/113) Mice with spontaneous pancreatic cancer naturally develop MUC-1-specific CTLs that eradicate tumors when adoptively transferred.

Pancreatic cancer is a highly aggressive, treatment refractory cancer and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas overexpress altered forms of a tumor-specific Ag, mucin 1 (MUC1; an epithelial mucin glycoprotein), which is a potential target for immunotherapy. We have established a clinically relevant animal model for pancreatic cancer by developing a double transgenic mouse model (called MET) that expresses human MUC1 as self molecule and develops spontaneous tumors of the pancreas. These mice exhibit acinar cell dysplasia at birth, which progresses to microadenomas and acinar cell carcinomas. The tumors express large amounts of underglycosylated MUC1 similar to humans. Tumor-bearing MET mice develop low affinity MUC1-specific CTLs that have no effect on the spontaneously occurring pancreatic tumors in vivo. However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity. These CTLs were MHC class I restricted and recognized peptide epitopes in the immunodominant tandem repeat region of MUC1. The MET mice appropriately mimic the human condition and are an excellent model with which to elucidate the native immune responses that develop during tumor progression and to develop effective antitumor vaccine strategies.  (+info)

(3/113) Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis.

Alterations of K- ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPMT), 6 acinar carcinomas (PAC), 5 solid-pseudopapillary tumours (SPT), 16 ampulla of Vater cancers (AVC) and 41 PET. All tumours were also presently or previously analysed for K- ras and p53 mutations and allelic loss at 9p, 17p and 18q. Alterations in K- ras, p53, p16 and DPC4 were found in 82%, 53%, 38% and 9% of PDC, respectively and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were virtually absent in PET, PAC or SPT, while in IPMT only K- ras mutations were present (30%). Positive immunostaining confirmed the absence of DPC4 alterations in all IPMT, SPT, PAC and PET, while 47% of PDC and 38% of AVC were immunonegative. These data suggest that pancreatic exocrine and endocrine tumourigenesis involves different genetic targets and that among exocrine pancreatic neoplasms, only ductal and ampullary cancers share common molecular events.  (+info)

(4/113) Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway.

Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/beta-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/beta-catenin pathway and for allelic loss on chromosome 11p. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome 11p was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the beta-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.  (+info)

(5/113) Primary acinic cell carcinoma of the breast.

Seven cases of this rare variant of breast carcinoma have been described in three previous publications. This paper describes an additional case, the first following chemotherapy, which in addition had an unfavourable prognosis. It also describes alterations in cell morphology, immunohistochemistry, and ultrastructure following chemotherapy.  (+info)

(6/113) Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency.

Apc (adenomatous polyposis coli) encodes a tumour suppressor gene that is mutated in the majority of colorectal cancers. Recent evidence has also implicated Apc mutations in the aetiology of breast tumours. Apc is a component of the canonical Wnt signal transduction pathway, of which one target is Tcf-1. In the mouse, mutations of both Apc and Tcf-1 have been implicated in mammary tumorigenesis. We have conditionally inactivated Apc in both the presence and absence of Tcf-1 to examine the function of these genes in both normal and neoplastic development. Mice harbouring mammary-specific mutations in Apc show markedly delayed development of the mammary ductal network. During lactation, the mice develop multiple metaplastic growths which, surprisingly, do not spontaneously progress to neoplasia up to a year following their induction. However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma.  (+info)

(7/113) Clinical characteristics and outcomes from an institutional series of acinar cell carcinoma of the pancreas and related tumors.

PURPOSE: Acinar cell carcinoma is a rare tumor of the exocrine pancreas. Clinical features such as prognostic information, survival, and treatment outcomes are unknown. We present the largest retrospective review to date. PATIENTS AND METHODS: Thirty-nine patients with pathologically confirmed acinar neoplasms of the pancreas were identified between August 1981 and January 2001. Demographic data, tumor characteristics, and treatment information were obtained by chart review. Survival probabilities were estimated by using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The median survival for all patients was 19 months. On the basis of a univariate analysis, the patients' stage of disease correlated significantly with survival. The median survival of patients with localized disease was 38 months, versus 14 months for those presenting with metastases (P = 0.03). Patients who could be treated with surgery as first-line therapy had a longer survival time (36 months) compared with those who did not have surgery (14 months). Two of 18 patients who received chemotherapy and three of eight patients who received radiation had a major response. CONCLUSION: The survival curves suggest a more aggressive cancer than pancreatic endocrine neoplasms but one that is less aggressive than ductal adenocarcinoma of the pancreas. Those patients who present with localized disease have a much better prognosis than those who present with metastases. There is a high recurrence rate after complete surgical resection, suggesting that micrometastases are present even in localized disease and that adjuvant therapies may be indicated. Chemotherapy and radiation afford disappointing results, however, and novel therapies are needed.  (+info)

(8/113) Exocrine pancreatic carcinogenesis in the guppy Poecilia reticulata.

Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following exposure to the direct-acting carcinogen methylazoxymethanol acetate (MAM-Ac). Fish 6 to 10 d old were exposed to nominal, non-toxic concentrations of 4 and 10 mg MAM-Ac l(-1) for 2 h and then transferred to carcinogen-free water for grow-out. Whole specimens were sampled monthly up to 9 mo post-exposure to follow the histologic progression of the lesions. No neoplasms occurred in 119 control specimens examined. Pancreatic acinar cell adenomas and carcinomas occurred in 42 of 243 (17%) of the specimens exposed to MAM-Ac. As in earlier studies, specimens exposed to the low MAM-Ac concentration exhibited a higher pancreatic neoplasm incidence (27.8%) than those exposed to the high concentration (7.8%). Acinar cell adenomas accounted for 27 of the 42 neoplasms. Adenomas exhibited a high degree of acinar cell differentiation and some contained foci of atypical acinar cells that were less differentiated and more basophilic than were surrounding adenoma cells. Carcinomas occurred in 15 specimens and exhibited a range of cellular patterns. Although no distant metastases were found, carcinomas tended to invade neighboring tissues and organs. The occurrence of carcinogen-induced pancreatic neoplasms in guppies strengthens the usefulness of small fish species in carcinogen testing and provides an additional model for studying pancreatic neoplasia.  (+info)