High stathmin expression is a marker for poor clinical outcome in endometrial cancer: An NRG oncology group/gynecologic oncology group study

• Published in: Gynecologic oncology Vol. 146; no. 2; pp. 247 - 253
• Main Authors: Reyes, Henry D, Miecznikowski, Jeffrey, Gonzalez-Bosquet, Jesus, Devor, Eric J, Zhang, Yuping, Thiel, Kristina W, Samuelson, Megan I, McDonald, Megan, Stephan, Jean-Marie, Hanjani, Parviz, Guntupalli, Saketh, Tewari, Krishnansu S, Backes, Floor, Ramirez, Nilsa, Fleming, Gini F, Filiaci, Virginia, Birrer, Michael J, Leslie, Kimberly K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2017
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides - metabolism; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - mortality; Carcinoma, Endometrioid - pathology; Carcinoma, Endometrioid - therapy; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Endometrial Neoplasms - therapy; Female; Hematology, Oncology and Palliative Medicine; Humans; Hysterectomy; Immunohistochemistry; Middle Aged; Neoplasm Staging; Obstetrics and Gynecology; Paclitaxel; Paclitaxel - administration & dosage; Piperidines - metabolism; Prognosis; Retrospective Studies; Stathmin; Stathmin - genetics; Stathmin - metabolism; Survival Rate; Stathmin; Endometrial cancer; Paclitaxel
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2017.05.017

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.