Citations

Abstract Background: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN). Methods: Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months. Results: Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC. Conclusions: SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival. Impact: SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC. Cancer Epidemiol Biomarkers Prev; 22(10); 1730–5. ©2013 AACR.

There has been an overall decline in the United States incidence of Primary CNS Lymphoma (PCNSL) from 1998 to 2008. This study's intent was to characterize the cohorts contributing to it. First, calculated the PCNSL incidence rates from nine Surveillance, Epidemiology, and End Results (SEER) registries for time period 1973 to 2008. Second, examined the time trends overall and by age and gender. Third, used 1992–2008 SEER data from the same registries to obtain overall trends for diffuse large B‐cell lymphoma (DLBCL). Last, rates were age‐adjusted to the 2000 US standard population and reported per 100,000 person‐years. Rates continued to increase in women at all ages and men aged 65 and older. In men aged 20–39 and 40–64 years incidence rates peaked in 1995 and then declined dramatically, stabilizing after 1998. The trends in the incidence of PCNSL over this time frame were significantly different from DLBCL for ages 20–39 (P < 0.001) and 40–64 (P < 0.001) years but were not different for the 65 years and older age group (P = 0.99). The overall PCNSL incidence rate declined since 1995 and was driven primarily by the changing incidence in young and middle‐aged men. The rate has continued to increase in men aged 65 years and older and in women. The trends in incidence in the younger age groups over this time period did not parallel those observed for DLBCL. Am. J. Hematol. 88:997–1000, 2013. © 2013 Wiley Periodicals, Inc.

Abstract Purpose: MUC1 is a tumor-associated antigen that is aberrantly expressed in cancer and inflammatory bowel disease (IBD). Even though immune cells express low MUC1 levels, their modulations of MUC1 are important in tumor progression. Consistent with previous clinical data that show increased myeloid-derived suppressor cells (MDSCs) in IBD, we now show that downregulation of MUC1 on hematopoietic cells increases MDSCs in IBD, similar to our data in tumor-bearing mice. We hypothesize that MDSC expansion in IBD is critical for tumor progression. Experimental Design: To mechanistically confirm the linkage between Muc1 downregulation and MDSC expansion, we generated chimeric mice that did not express Muc1 in the hematopoietic compartment (KO→WT). These mice were used in two models of colitis and colitis-associated cancer (CAC) and their responses were compared with wild-type (WT) chimeras (WT→WT). Results: KO→WT mice show increased levels of MDSCs during colitis and increased protumorigenic signaling in the colon during CAC, resulting in larger colon tumors. RNA and protein analysis show increased upregulation of metalloproteinases, collagenases, defensins, complements, growth factors, cytokines, and chemokines in KO→WT mice as compared with WT→WT mice. Antibody-mediated depletion of MDSCs in mice during colitis reduced colon tumor formation during CAC. Conclusion: Development of CAC is a serious complication of colitis and our data highlight MDSCs as a targetable link between inflammation and cancer. In addition, the lack of MUC1 expression on MDSCs can be a novel marker for MDSCs, given that MDSCs are still not well characterized in human cancers. Clin Cancer Res; 19(18); 5039–52. ©2013 AACR.