Volume-Based Care among Young Women Diagnosed with Uterine Cancer

Purpose. To characterize volume-based care of uterine cancer among women aged ≤50 years. Methods. The Maryland Health Service Cost Review Commission database was accessed for uterine cancer surgical cases from 1994 to 2005. Cross-tabulations and logistic regression models were used to evaluate for significant associations among volume-based care and other variables comparing women ≤50 years with those aged >50 years. Results. Women ≤50 years comprised 13.6% of the cases. Women ≤50 years were less likely to be managed by high-volume surgeons (31.6% versus 35.1%, P = 0.02). For women ≤50 years, there was a trend toward management at low-volume hospitals (52.0% versus 54.0%, P = 0.22). No deaths were reported among the group of women ≤50 years treated by high-volume providers or at high-volume centers. Women ≤50 years managed by high-volume surgeons had longer length of stay (P < 0.001) and higher adjusted cost of hospital-related care (P < 0.00). Women ≤50 years managed at high-volume centers had higher adjusted cost of hospital-related care (P = 0.01). Conclusion. Primary surgical care of young women with uterine cancer is often performed by low-volume providers

Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.</p> <p>Methods</p> <p>A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged <it>in vivo </it>by intraperitoneal injection into immunocompetent Lewis rats, and <it>in vitro </it>culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. β-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.</p> <p>Results</p> <p>The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line <it>in vitro</it>, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear β-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.</p> <p>Conclusion</p> <p>This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.</p

Alterations in Mucin Expression in Ovarian Mucinous Tumors: Immunohistochemical Analysis of MUC2, MUC5AC, MUC6, and CD10 Expression

The aim of this study was to evaluate the immunohistochemical expression of MUC2, MUC5AC, MUC6, and CD10 in ovarian mucinous adenoma (MA), mucinous borderline tumor (MB), and mucinous adenocarcinoma (MC), and to analyze the relationship between prognosis and these expressions. The expression of MUC2, MUC5AC, MUC6, and CD10 was evaluated by immunohistochemical analysis in 29 cases of MA, 29 cases of MB, and 26 cases of MC and scored based on the percentage of positive cells. Moreover, the ovarian mucinous tumors were classified into 4 phenotypes based on the staining patterns: intestinal, gastrointestinal, gastric, and unclassified patterns. The gastrointestinal pattern and the expression of MUC2 and CD10 increased from MA to MC. Conversely, the gastric pattern and MUC5AC expression decreased from MA to MC. Low MUC2 expression in MC was correlated with a better long-term survival rate. MUC2 expression in MC may be a useful predictor of the clinical outcome. The expression patterns of MUC2, MUC5AC, MUC6, and CD10 indicated that intestinal metaplasia may arise from the gastric-like epithelium in MA and that a close association exists between carcinogenesis and intestinal metaplasia in major ovarian mucinous tumors

Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Ovarian cancer molecular pathology.

Peer reviewe

Role of adjuvant chemotherapy in the management of stage IC ovarian granulosa cell tumors

Objective: The aim of the present study was to investigate the patterns of use and prognostic significance of adjuvant chemotherapy (CT) for patients with stage IC ovarian granulosa cell tumors (GCTs). Methods: We identified patients with stage IC GCTs diagnosed between 2004 and 2015 in the National Cancer Data Base (NCDB). Logistic regression was performed to identify variables independently associated with chemotherapy administration. Overall survival (OS) was evaluated for patients diagnosed between 2004 and 2014 following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for known confounders. Results: A total of 492 patients with stage IC GCTs were identified, of which 166 (33.7%) received CT. Tumor size > = 10 cm (OR: 1.85, 95% CI: 1.21, 2.82) was independently associated with the administration of CT. There was no difference in OS between patients who did (n = 145) and did not (n = 282) receive CT, p = 0.52; 5-yr OS rates were 93.7% and 91.6% respectively. After controlling for patient age (<50 vs ≥50 years), tumor size and performance of lymphadenectomy (LND), the administration of CT was not associated with a survival benefit (HR: 1.07, 95% CI: 0.52, 2.21). Conclusions: Approximately one in three patients with stage IC GCTs received CT in the NCDB, however CT was not associated with a survival benefit. Keywords: Ovary, Tumor, Chemotherapy sex cord-stromal, Granulosa cel