Abstract
ObjectiveGynecologic 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. MethodsWe 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. ResultsWe 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. ConclusionsOur 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.
Highlights
Endometrial cancer is the most common gynecologic malignancy in women [1]
Using 333 identified endometrial cancer patients from The Cancer Genome Atlas (TCGA) database (271 endometrioid and 62 serous), we examined the relationship of STMN1 gene expression with overall survival (OS) and progression-free survival (PFS)
Stathmin overexpression predicts for poorer overall survival and progression-free survival
Summary
Endometrial cancer is the most common gynecologic malignancy in women [1]. Early stage disease can be treated surgically, with some cases receiving radiation treatment to decrease local and regional recurrence. GOG-177 was a phase III randomized controlled trial that enrolled patients with advanced (stage III or IV) or recurrent endometrial cancer between two treatment arms: adriamycin (doxorubicin)/cisplatin (AP) vs adriamycin/cisplatin/paclitaxel with G-CSF (TAP). Results from this trial showed that patients treated with the three-drug regimen TAP had a better overall response rate (57% vs 34%), median progression-free survival (PFS) (8.3 vs 5.3 months), and median overall survival (OS) (15.3% vs 12.3%) [1]. GOG177 and GOG-209 have defined the modern therapeutic treatment for advanced and recurrent endometrial cancer
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