Koji Matsuo1, Todd B Sheridan2, Seiji Mabuchi3, Kiyoshi Yoshino3, Kosei Hasegawa4, Kimberley D Studeman2, Dwight D Im5, Neil B Rosenshein5, Lynda D Roman6, Anil K Sood7. 1. 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. 2. Department of Pathology, Mercy Medical Center, Baltimore, MD, USA. 3. Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Suita, Osaka, Japan. 4. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. 5. Gynecologic Oncology Center, Mercy Medical Center, Baltimore, MD, USA. 6. 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. 7. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Laura M Divine; Nora T Kizer; Andrea R Hagemann; Meredith E Pittman; Ling Chen; Matthew A Powell; David G Mutch; Janet S Rader; Premal H Thaker Journal: Gynecol Oncol Date: 2016-05-08 Impact factor: 5.482