CD55 is a membrane complement regulatory protein that attenuates complement-mediated cytotoxicity. Saygin et al. elucidate a new role for CD55 as a signaling hub for cancer stem cell self-renewal and cisplatin resistance pathways in endometrioid tumors and open a new line of research into chemotherapeutic-refractory cancers.

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This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.

Granulin-epithelin precursor (GEP/progranulin) is an autocrine growth factor for ovarian cancer. We examined the production and function of GEP and report that: (1) GEP production is regulated by endothelin (ET-1), lysophosphatidic acid (LPA), and cAMP; (2) cAMP signals GEP production through exchange protein activated by cAMP (EPAC); (3) ET-1 and cAMP/EPAC induce GEP through ERK1/2; and (4) neutralization of GEP results in apoptosis. Exposure of HEY-A8 and OVCAR3 ovarian cancer cells to LPA and ET-1 yielded GEP production and secretion in a dose-and timedependent fashion; neither stimulated significant concentrations of cAMP directly. Stimulation of cAMP production with pertussis and cholera toxin, or forskolin induced GEP in a PKA-independent fashion. EPAC, an intracellular cAMP receptor, is activated specifically by the cAMP analog, 8-CPT-2 0 -O-Me-cAMP (8-CPT); 8-CPT treatment stimulated GEP production and secretion. The MEK inhibitor, U0126, abrogated GEP production in response to ET-1 and 8-CPT, confirming involvement of MAPK. A partial inhibition of basal and stimulated GEP production was observed when cells were treated with a internal calcium chelator, BAPTA. Neutralizing anti-GEP antibody reversed basal as well as LPA, ET-1 and 8-CPT-induced ovarian cancer cell growth and induced apoptosis as demonstrated by caspase-3 and PARP cleavage, DNA fragmentation, and nuclear condensation. These results indicate that GEP is a growth and survival factor for ovarian cancer, induced by LPA and ET-1 and cAMP/EPAC through ERK1/2. Oncogene (2005) 24, 7084-7093.

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Seven percent of patients undergoing laparotomy for gynecologic malignancy developed SSI. Surgical site infection is associated with longer hospital stay and more than 5-fold increased risk of reoperation. In this study, we identified several risk factors for developing SSI among gynecologic cancer patients. These findings may contribute toward identification of patients at risk for SSI and the development of strategies to reduce SSI rate and potentially reduce the cost of care in gynecologic cancer surgery.

Background Endometrial cancer (EC) has only been recently recognized as a major component in Cowden syndrome (CS). Germline PTEN (PTEN_mut+), SDHB-D (SDHx_var+) and KLLN (KLLN_Me+) alterations cause CS and CS-like (CSL) phenotypes. This study aims to identify prevalence and clinico-pathologic predictors of germline PTEN_mut+, SDHx_var+ or KLLN_Me+ in CS/CSL patients presenting with EC. Methods PTEN and SDHB-D mutation and KLLN promoter methylation analyses were performed on 371 prospectively enrolled (2005–2011) patients. PTEN protein was analyzed from patient-derived lymphoblast lines. PTEN Cleveland Clinic score (CC score) is a weighted regression-based risk calculator that gives a priori risk of PTEN_mut+. Demographic and clinicopathologic features were correlated with specific gene. Results Germline PTEN_mut+, SDHx_var+ and KLLN_Me+ were found in 7%, 9.8% and 10.5% of informative samples, respectively. Predictors of PTEN_mut+ included age≤50 (OR6.1, p=0.015 for age<30, OR4.4, p=0.001 for age 30–50), macrocephaly (OR14.4, p<0.001), higher CC score (OR1.35 for 1 unit increment, p<0.001), PTEN protein level at the lowest quartile (OR5.1, p=0.039) and coexisting renal cancer (OR5.7, p=0.002). KLLN_Me+ patients were a mean 8 years younger than KLLN_Me− ones (44 vs. 52, p=0.018). Predictors of KLLN_Me+ were younger age and higher CC score. On the other hand, no clinical predictors of SDH_var+ were found. Conclusions We identified clinical predictors of PTEN and KLLN alterations, but not SDHx_var+. Having these predictors should alert the treating physician to potential heritable risk for referral to genetic professionals. High-risk cancer surveillance and prophylactic surgery of the uterus may be considered for KLLN_Me+ similar to PTEN_mut+ patients.

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