Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 875 Blake Wilbur Drive, MC 5827, Stanford, CA 94305, USA.
British Journal of Cancer (Impact Factor: 4.84). 04/2006; 94(5):642-6. DOI: 10.1038/sj.bjc.6603012
Source: PubMed


To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan-Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P<0.0001) and more likely to be black compared to G3EC (15 and 12% vs 7%; P<0.0001). A higher proportion of UPSC and CC patients had stage III-IV disease compared to G3EC patients (52 and 36% vs 29%; P<0.0001). Uterine papillary serous carcinoma, CC and G3EC patients represent 10, 3, and 15% of endometrial cancers but account for 39, 8, and 27% of cancer deaths, respectively. The 5-year disease-specific survivals for women with UPSC, CC and G3EC were 55, 68, and 77%, respectively (P<0.0001). The survival differences between UPSC, CC and G3EC persist after controlling for stage I-II (74, 82, and 86%; P<0.0001) and stage III-IV disease (33, 40, and 54; P<0.0001). On multivariate analysis, more favourable histology (G3EC), younger age, and earlier stage were independent predictors of improved survival. Women with UPSC and CC of the uterus have a significantly poorer prognosis compared to those with G3EC. These findings should be considered in the counselling, treating and designing of future trials for these high-risk patients.

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Available from: Michael Hendrickson, Jan 20, 2015
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    • "While early stage, low grade EEC is classically managed by curative hysterectomy, latestage EEC/type II endometrial cancers are associated with significant mortality due to their metastatic spread outwith the uterine corpus (Dedes et al, 2011; DeLeon et al, 2014). Difficulties still exist with the type I/II classification system in terms of prognosis: there is uncertainty as to whether grade 3 EECs should be classified as type I or type II carcinomas (Boruta et al, 2004; Hamilton et al, 2006; Soslow et al, 2007; Voss et al, 2012) while the prognostic significance of tumours with mixed type I/II histology remains the subject of debate (Patsavas et al, 2011; Roelofson et al, 2012). The existence of grade 1 EECs arising in a background of atrophic endometrium also presents difficulties for this dualistic model (Geels et al, 2012). "
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    ABSTRACT: Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer. Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan-Meier analysis. Receiver-operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests. Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001). Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.British Journal of Cancer advance online publication, 16 June 2015; doi:10.1038/bjc.2015.200
    British Journal of Cancer 06/2015; 113(2). DOI:10.1038/bjc.2015.200 · 4.84 Impact Factor
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    • "These tumors are typically well differentiated, minimally invasive into the uterine wall, generally estrogen dependent, and have a good prognosis . In contrast, type II tumors, which are typically poorly differentiated, occur in older women, are usually diagnosed at advanced stage of the disease, and are characterized by an aggressive behavior and a worse prognosis (Hamilton et al., 2006). Uterine serous carcinoma (USC) constitutes the predominant histological class among type II tumors. "
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    ABSTRACT: Insulin analogues have been developed to achieve further improvement in the therapy of diabetes. However, modifications introduced into the insulin molecule may enhance their affinity for the insulin-like growth factor-1 receptor (IGF1R). Hyperinsulinemia has been identified as a risk factor for endometrial cancer. We hypothesized that insulin analogues may elicit atypical proliferative and signaling activities in endometrial cancer cells. Our results demonstrate that glargine, but not detemir, stimulated cell proliferation, displayed an anti-apoptotic effect, and had a positive effect on cell cycle progression in endometrial cancer cell lines ECC-1 and USPC-1. In addition, we showed that glargine and detemir induced dual activation of the insulin receptor (INSR) and IGF1R in both cell types. Furthermore, we showed that glargine elicited signaling events that are markedly different from those induced by insulin. In conclusion, our data support the concept that, although insulin analogues were designed to display insulin-like metabolic effects, glargine and, possibly, additional analogues exhibit IGF1-like activities and, accordingly, may function as IGF1 analogues. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 02/2015; 406. DOI:10.1016/j.mce.2015.02.011 · 4.41 Impact Factor
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    • "Please cite this article as: Growdon WB, et al, HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant, Gynecol Oncol (2015), EnCa encountered, this high grade subset accounts for the majority of the 8000 deaths observed annually and innovative, targeted therapies are needed to improve outcomes [3]. Amplification of the HER2 gene and over-expression of the HER2 protein have been described in many human malignancies including breast, colon, gastric, esophageal and endometrial and for some of these cancers, anti-HER2 therapies have become a mainstay of treatment [4] [5] [6]. "
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    ABSTRACT: Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000-2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest®), HER2 fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag® testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8 RF/mm(2) was observed in 53% (n=54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p<0.001). These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Gynecologic Oncology 01/2015; 63(1). DOI:10.1016/j.ygyno.2015.01.533 · 3.77 Impact Factor
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