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

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.

• Authors: Henry D Reyes, Jeffrey Miecznikowski, Jesus Gonzalez-Bosquet, Eric J Devor, Yuping Zhang, Kristina W Thiel, Megan I Samuelson, Megan McDonald, Jean-Marie Stephan, Parviz Hanjani, Saketh Guntupalli, Krishnansu S Tewari, Floor Backes, Nilsa Ramirez, Gini F Fleming, Virginia Filiaci, Michael J Birrer, Kimberly K Leslie
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 146 Issue 2 Pg. 247-253 (08 2017) ISSN: 1095-6859 [Electronic] United States
• PMID: 28532857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Benzamides
• N-phenyl-N-(1-(piperidine-1-carbonyl)cyclohexyl)benzamide
• Piperidines
• STMN1 protein, human
• Stathmin
• Doxorubicin
• Paclitaxel
• Cisplatin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzamides (metabolism)
• Carcinoma, Endometrioid (genetics, mortality, pathology, therapy)
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Endometrial Neoplasms (genetics, mortality, pathology, therapy)
• Female
• Humans
• Hysterectomy
• Immunohistochemistry
• Middle Aged
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Piperidines (metabolism)
• Prognosis
• Retrospective Studies
• Stathmin (genetics, metabolism)
• Survival Rate