Henry D Reyes1, Jeffrey Miecznikowski2, Jesus Gonzalez-Bosquet3, Eric J Devor4, Yuping Zhang5, Kristina W Thiel6, Megan I Samuelson7, Megan McDonald8, Jean-Marie Stephan9, Parviz Hanjani10, Saketh Guntupalli11, Krishnansu S Tewari12, Floor Backes13, Nilsa Ramirez14, Gini F Fleming15, Virginia Filiaci16, Michael J Birrer17, Kimberly K Leslie18. 1. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: henry-reyes@uiowa.edu. 2. Department of Biostatistics, SUNY University at Buffalo, Buffalo, NY, USA. Electronic address: jcm38@buffalo.edu. 3. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: jesus-gonzalezbosquet@uiowa.edu. 4. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: eric-devor@uiowa.edu. 5. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: Yuping-zhang@uiowa.edu. 6. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: Kristina-thiel@uiowa.edu. 7. Department of Pathology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: megan-samuelson@uiowa.edu. 8. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: megan-e-mcdonald@uiowa.edu. 9. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: jean-marie-stephan@uiowa.edu. 10. Department of Gynecologic Oncology, Hanjani Institute for Gynecologic Oncology, Abington Memorial Hospital, Abington, PA, USA. Electronic address: phanjani@amh.org. 11. Department of Obstetrics & Gynecology, University of Colorado - Denver, Aurora, CO, USA. Electronic address: saketh.guntupalli@ucdenver.edu. 12. Division of Gynecologic Oncology, University of California, Irvine Medical Center, Orange, CA, USA. Electronic address: ktewari@uci.edu. 13. Department/Division of Obstetrics & Gynecology, Ohio State University Medical Center, Columbus, OH, USA. Electronic address: floor.backes@osumc.edu. 14. Department of Pathology, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: nilsa.ramirez@nationwidechildrens.org. 15. Section of Medical Oncology, University of Chicago, Chicago, IL, USA. Electronic address: gfleming@medicine.bsd.uchicago.edu. 16. Biostatistics & Data Center, NRG Oncology/Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: gfiliaci@gogstats.org. 17. Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: mbirrer@partners.org. 18. Department of Obstetrics & Gynecology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: Kimberly-Leslie@uiowa.edu.
Abstract
OBJECTIVE: Gynecologic Oncology Group (GOG) 177 demonstrated that addition of paclitaxel to a backbone of adriamycin/cisplatin improves overall survival (OS) and progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer. Using patient specimens from GOG-177, our objective was to identify potential mechanisms underlying the improved clinical response to taxanes. Stathmin (STMN1) is a recognized poor prognostic marker in endometrial cancer that functions as a microtubule depolymerizing protein, allowing cells to transit rapidly through mitosis. Therefore, we hypothesized that one possible mechanism underlying the beneficial effects of paclitaxel could be to counter the impact of stathmin. METHODS: We analyzed the expression of stathmin by immunohistochemistry (IHC) in 69 specimens from patients enrolled on GOG-177. We also determined the correlation between stathmin mRNA expression and clinical outcomes in The Cancer Genome Atlas (TCGA) dataset for endometrial cancer. RESULTS: We first established that stathmin expression was significantly associated with shorter PFS and OS for all analyzed cases in both GOG-177 and TCGA. However, subgroup analysis from GOG-177 revealed that high stathmin correlated with poor PFS and OS particularly in patients who received adriamycin/cisplatin only. In contrast, there was no statistically significant association between stathmin expression and OS or PFS in patients treated with paclitaxel/adriamycin/cisplatin. CONCLUSIONS: Our findings demonstrate that high stathmin expression is a poor prognostic marker in endometrial cancer. Paclitaxel may help to negate the impact of stathmin overexpression when treating high risk endometrial cancer cases.
OBJECTIVE: Gynecologic Oncology Group (GOG) 177 demonstrated that addition of paclitaxel to a backbone of adriamycin/cisplatin improves overall survival (OS) and progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer. Using patient specimens from GOG-177, our objective was to identify potential mechanisms underlying the improved clinical response to taxanes. Stathmin (STMN1) is a recognized poor prognostic marker in endometrial cancer that functions as a microtubule depolymerizing protein, allowing cells to transit rapidly through mitosis. Therefore, we hypothesized that one possible mechanism underlying the beneficial effects of paclitaxel could be to counter the impact of stathmin. METHODS: We analyzed the expression of stathmin by immunohistochemistry (IHC) in 69 specimens from patients enrolled on GOG-177. We also determined the correlation between stathmin mRNA expression and clinical outcomes in The Cancer Genome Atlas (TCGA) dataset for endometrial cancer. RESULTS: We first established that stathmin expression was significantly associated with shorter PFS and OS for all analyzed cases in both GOG-177 and TCGA. However, subgroup analysis from GOG-177 revealed that high stathmin correlated with poor PFS and OS particularly in patients who received adriamycin/cisplatin only. In contrast, there was no statistically significant association between stathmin expression and OS or PFS in patients treated with paclitaxel/adriamycin/cisplatin. CONCLUSIONS: Our findings demonstrate that high stathmin expression is a poor prognostic marker in endometrial cancer. Paclitaxel may help to negate the impact of stathmin overexpression when treating high risk endometrial cancer cases.
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Authors: Henrica M J Werner; Jone Trovik; Mari K Halle; Elisabeth Wik; Lars A Akslen; Even Birkeland; Therese Bredholt; Ingvild L Tangen; Camilla Krakstad; Helga B Salvesen Journal: PLoS One Date: 2014-02-25 Impact factor: 3.240
Authors: Anthony N Karnezis; Samuel Leung; Jamie Magrill; Melissa K McConechy; Winnie Yang; Christine Chow; Martin Kobel; Cheng-Han Lee; David G Huntsman; Aline Talhouk; Friederich Kommoss; C Blake Gilks; Jessica N McAlpine Journal: J Pathol Clin Res Date: 2017-10-14