p-21-Activated kinase-1, -4 and -6 and estrogen receptor expression pattern in normal placenta and gestational trophoblastic diseases |
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| Authors: | Melina Shoni Zoltan Nagymanyoki Allison F Vitonis Cynthia Jimenez Shu-Wing Ng Bradley J Quade Ross S Berkowitz |
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| Institution: | 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women''s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;2. Division of Women''s and Perinatal Pathology, Department of Pathology, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA, USA;3. Donald P Goldstein, MD Trophoblastic Tumor Registry, New England Trophoblastic Disease Center, MA, USA |
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| Abstract: | ObjectivesTo delineate the potential role of p21-activated kinases (PAKs) in the pathogenesis of gestational trophoblastic diseases (GTD) by defining the expression pattern of PAK-1, -4 and -6 and their potential implication in estrogen receptor (ER) regulation of normal placental tissue and GTD.MethodsWe evaluated immunohistochemically 10 normal first-trimester placentas (NP), 10 partial moles (PM), 15 complete moles (CM) and 3 choriocarcinomas (CCA) for PAK-1, PAK-4, PAK-6 and ER expression intensity and localization. Staining outcomes were assessed utilizing non-parametric Kruskal–Wallis one-way analysis of variance test followed by pairwise Wilcoxon Rank Sum tests. Statistical significance was determined by two-sided p-value of < 0.05.ResultsIn NP, PAK-6 immunoreactivity was predominantly cytoplasmic. Compared to NP, PM and CM demonstrated significant increase of cytoplasmic PAK-6 in cytotrophoblast (p = 0.012, p = 0.033 respectively), accompanied by significantly increased nuclear immunoreactivity in cytotrophoblast (p = 0.008, p = 0.045 respectively) and intermediate trophoblast (p = 0.003, p = 0.015 respectively). PAK-4 was found significantly upregulated in both cytoplasmic and nuclear compartments of cytotrophoblast and syncytiotrophoblast in PM (p = 0.004 and p = 0.002 for cytotrophoblast; p = 0.018 and p = 0.002 for syncytiotrophoblast, respectively) and CM (p = 0.001 and p = 0.001 for cytotrophoblast; p = 0.002 and p = 0.001 for syncytiotrophoblast, respectively) when compared to NP, whereas PAK-1 expression was significantly reduced in the syncytiotrophoblast of PM (p = 0.025 for cytoplasm and p = 0.008 for nucleus). Nuclear expression of ER was undetectable in all stained samples.ConclusionOur results reveal PAK-6 upregulation in GTD compared to NP. The absence of nuclear expression of ER might stem in part from the repressive effect of PAK-6 in trophoblastic tissue. |
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| Keywords: | Gestational trophoblastic diseases p-21-Activated Kinases PAK-6 Estrogen receptors |
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