A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemcitabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma
L. DuskaGina R. PetroniJubilee BrownD. JelovacK.N. MooreWilliam P. McGuireChristopher J. DarusLisa BarroilhetAngeles Alvarez Secord
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Pazopanib
Fallopian tube
Fallopian tube cancer is a rare tumor which accounts for only 1% of all gynaecological cancers. It is closely related and generally treated with a similar approach to ovarian cancer. We used the publicly available databases to provide a description of epidemiological patterns, clinical outcomes, and mutational landscape of fallopian tube cancer and compare it with that of ovarian cancer. We extracted clinical and epidemiological data of fallopian tube and ovarian cancers from the SEER database [13 reg; Nov 2020 Submission]. The average annual percentage change (AAPC) of incidence rates was calculated using The NIH's Joinpoint Regression Program. Sequencing data were obtained through The American Association of Cancer Research (AACR) project GENIE database. We included 4,240 cases of fallopian tube cancer and 74,837 cases of ovarian cancer diagnosed between 1992 and 2018. The overall incidence of fallopian tube cancer was 0.39 [95% CI, 0.38-0.40], whereas the overall incidence of ovarian cancer was 6.97 [95% CI, 6.92-7.02]. Between 1992 and 2018, there was a significant increase in the incidence of fallopian tube cancer (AAPC = 6.1% 95% CI, [4.6, 7.9], p<0.001) and a decrease in the incidence of Ovarian cancer (AAPC = -1.7% 95% CI, [-2, -1.4], p<0.001). The median overall survival of fallopian tube cancer was significantly higher than ovarian cancer (80 months vs 43 months, P<0.001). A presentation with stage IV disease was significantly less frequent in fallopian tube cancer compared to ovarian cancer (50% vs 70%, P<0.001). In 166 patients with fallopian tube cancer and 5,303 patients with ovarian cancer in GENIE, the most frequently mutated genes were TP53, SPTA1, LRP1B, FAT3, and NF1; and TP53, CSMD3, DNAH9, ARID1A, and PDE4DIP; for fallopian tube cancer and ovarian cancer respectively. Fallopian tube cancer is a distinct disease entity different in genetic, epidemiological, and clinical characteristics from ovarian cancer. Cases with fallopian tube cancer are less likely to present with distant metastasis and have longer overall survival compared to cases with ovarian cancer. The most frequently mutated genes of both cancers are different.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding actin, beta-like 2, ACTBL2, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. ACTBL2 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. These data indicate that expression of ACTBL2 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. ACTBL2 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding prune homolog 2, PRUNE2, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. PRUNE2 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. PRUNE2 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of PRUNE2 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. PRUNE2 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding NK2 homeobox 1, NKX2-1, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. NKX2-1 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. NKX2-1 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of NKX2-1 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. NKX2-1 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding regulator of G-protein signaling 1, RGS1, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. RGS1 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. RGS1 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of RGS1 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. RGS1 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding solute carrier family 25 member 39, SLC25A39, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLC25A39 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. These data indicate that expression of SLC25A39 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLC25A39 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding solute carrier family 24 member 2, SLC24A2, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLC24A2 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLC24A2 expression correlated with progression-free survival in patients p53 mutant with ovarian cancer. These data indicate that expression of SLC24A2 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLC24A2 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding solute carrier family 24 member 3, SLC24A3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLC24A3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLC24A3 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of SLC24A3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLC24A3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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Fallopian tube cancer
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding ribophorin II, RPN2, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. RPN2 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. These data indicate that expression of RPN2 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. RPN2 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.
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