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Background: In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. Aims: To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. Methods: Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. Results: The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients.Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. Conclusion: Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.

Pancreatic cancer is characterized by aggressive growth and treatment resistance. New approaches include immunotherapeutic strategies but the type and extent of spontaneous immune responses against tumor antigens remains unclear. A dominance of TH2 cytokines in patients' sera reported previously suggests systemic tumor-induced immunosuppression, potentially inhibiting the induction of tumor-reactive T cells. We characterized the localization, frequencies, and functional potential of spontaneously induced memory T cells specific for individual tumor antigens or the tumor-associated antigen mucin-1 in the peripheral blood and bone marrow of 41 pancreatic cancer patients. We found high numbers of tumor-reactive T cells in all bone marrow samples and in 50% of the blood samples. These cells secreted the TH1 cytokine IFN-; rather than TH2 cytokines upon stimulation with tumor antigens. Although consistently induced during pancreatic cancer, T cells specific for pancreatic antigens were not detected during chronic pancreatitis, suggesting that their evaluation may be of diagnostic use in both diseases. Freshly isolated T cells from cancer patients recognized autologous tumor cells and rejected them in vitro and in a xenotransplant model in vivo, suggesting their therapeutic potential. Thus, tumor antigen-specific T cell responses occur regularly during pancreatic cancer disease and lead to enrichment of tumor cell-reactive memory T cells in the bone marrow. The bone marrow can therefore be considered an important organ for antitumor immune responses in pancreatic cancer. (Cancer Res 2005; 65(21): 10079-87)

Purpose: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor.We recently reported that after protein kinase C activation, colocalization of a6h4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. Experimental Design: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. Results: The majority of pancreatic and colorectal tumors expressed the a2, a3, a6, h1, and h4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of a6h4 and CO-029 was restricted to tumor cells, whereas a1, a2, a3, a6, h1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and h1expression was observed at comparably high levels in healthy pancreatic tissue. a3h1frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas a6h4 colocalized and coimmunoprecipitated mostly with CD151and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151and CO-029 with h4 and was accompanied by internalization of the integrintetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. Conclusion: a6h4 is selectively up-regulated in pancreatic and colorectal cancer. The association of a6h4 with CD151and CO-029 correlates with increased tumor cell motility.Pancreatic adenocarcinoma is a leading cause of cancer-related death and the frequency is increasing steadily (1). Patients with pancreatic adenocarcinoma have a very poor prognosis, the 1-year survival rate being <20% and the 5-year survival rate being <1% in most clinical centers. This is partly due to the fact that >80% of patients have massive metastatic spread at the time of diagnosis (1, 2). The early spread is proposed to proceed after settling of tumor cells in the peritoneal cavity and the penetration into blood vessels via so-called peritoneal pores, with formation of metastases preferentially in the liver (3). The mechanisms underlying the extraordinarily high invasive capacity of pancreatic adenocarcinoma are not yet understood. It is suggested that altered expression of adhesion molecules, particularly of integrins, might be an important factor (4).Changes in expression of integrins, particularly, a3h1 and a6h4, are frequently related to the metastatic capacity of tumor cells (5, 6). Reports on the integrin expression profile in pancreatic adenocarcinoma revealed partly contradictory results. It has been described that a2, a3, a5, a6, av, h1, and h4 are overexpressed in pancreatic adenocarcinoma lines, that do not express the a1, a4, or h2 integrins (7). High a6 expression on tumor tissue and w...