Faculty Bibliography

BACKGROUND:The diagnosis of serous cystadenoma (SCA), a rare benign pancreatic neoplasm, can alter the management of patients with pancreatic masses. Although characteristic imaging findings and fluid chemical analysis have been described, SCAs are not always recognized preoperatively. Furthermore, scant cellular yield on fine-needle aspiration (FNA) often leads to a nondiagnostic or nonspecific benign diagnosis. α-Inhibin (AI), a sensitive marker for SCA, is infrequently required for diagnosis in surgical specimens due to their characteristic histologic appearance. The objective of the current study was to determine whether AI staining can improve SCA diagnosis on FNA specimens. METHODS:Fifteen confirmed cases of SCA with prior FNA specimens were selected for this study. FNAs were evaluated for cellularity, cellular arrangement, and cytomorphology. Resection specimens were reviewed. RESULTS:Of the 15 FNA cases, approximately 75% demonstrated scant cellularity (11 of 15 cases). On smears, the cells were arranged as flat sheets, corresponding to strips of cells on cell block sections. The cells were small and round to cuboidal, with clear cytoplasm; occasional plasmacytoid cells and oncocytic cells were identified. Flattened cells, corresponding to attenuated epithelial cells lining macrocysts on the resections, were also noted. Stromal fragments were present in 5 FNAs and correlated with the hyalinized stroma in the resection specimens. AI immunostaining was positive in 88% of cases (7 of 8 of cases), thereby supporting the diagnosis of SCA. CONCLUSIONS:The results of the current study indicate that low cellularity and bland cytology are inherent to SCAs. Performing cell blocks and AI staining on FNA specimens is useful for establishing the diagnosis of SCA. An immunohistochemical panel including AI, chromogranin, and synaptophysin may enhance the diagnostic accuracy of pancreatic FNA specimens.

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.