title: Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma.
abstract: OBJECTIVE
  Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.
  
  
  METHODS
  Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.
  
  
  RESULTS
  LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r=0.31, p=0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p=0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p=0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54-5.88, p=0.001) and overall survival (HR 2.69, 95%CI 1.18-6.23, p=0.021) while ER-expression did not remain as a significant variable in multivariate analysis.
  
  
  CONCLUSIONS
  Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: koji.matsuo@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Pathology, Mercy Medical Center, Baltimore, MD, USA.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Sheridan
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, Mercy Medical Center, Baltimore, MD, USA.
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Studeman
authors.affiliation: Gynecologic Oncology Center, Mercy Medical Center, Baltimore, MD, USA.
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Im
authors.affiliation: Gynecologic Oncology Center, Mercy Medical Center, Baltimore, MD, USA.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Rosenshein
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: Lynda D
authors.initials: LD
authors.lastname: Roman
authors.affiliation: Department of Gynecologic Oncology, UT MD Anderson Cancer Center, Houston, TX, USA; Department of Cancer Biology, UT MD Anderson Cancer Center, Houston, TX, USA; Center for RNA Interference and non-Coding RNA, University of Texas, Houston, TX, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001808:Blood Vessels / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010388:Pelvis; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C513055:ABCB1 protein, human; C506487:ESR1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Estrogen receptor; High-grade serous ovarian carcinoma; Lymphovascular space invasion; Ovarian cancer