Département d'Anatomie Pathologique, Institut Salah Azaiez, Bab Saadoun, Tunis 1006, Tunisia.
Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR7258, Aix-Marseille Université, 13007 Marseille, France.
Int J Mol Sci. 2017 Dec 23;19(1):41. doi: 10.3390/ijms19010041.
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Identification of new therapeutic targets is crucial. MARCKS, myristoylated alanine-rich C-kinase substrate, has been implicated in aggressiveness of several cancers and MARCKS inhibitors are in development. Using immunohistochemistry (IHC), we retrospectively assessed MARCKS expression in epithelial and stromal cells of 118 pre-chemotherapy EOC samples and 40 normal ovarian samples from patients treated at Salah Azaiez Institute. We compared MARCKS expression in normal versus cancer samples, and searched for correlations with clinicopathological features, including overall survival (OS). Seventy-five percent of normal samples showed positive epithelial MARCKS staining versus 50% of tumor samples ( = 6.02 × 10). By contrast, stromal MARCKS expression was more frequent in tumor samples (77%) than in normal samples (22%; = 1.41 × 10). There was no correlation between epithelial and stromal IHC MARCKS statutes and prognostic clinicopathological features. Stromal MARCKS expression was correlated with shorter poor OS in uni- and multivariate analyses. Stromal MARCKS overexpression in tumors might contribute to cancer-associated fibroblasts activation and to the poor prognosis of EOC, suggesting a potential therapeutic interest of MARCKS inhibition for targeting the cooperative tumor stroma.
上皮性卵巢癌 (EOC) 是最致命的妇科癌症。寻找新的治疗靶点至关重要。MARCKS，肉豆蔻酰化的富含丙氨酸的 C 激酶底物，与几种癌症的侵袭性有关，并且 MARCKS 抑制剂正在开发中。我们使用免疫组织化学 (IHC) 方法，回顾性评估了 118 例化疗前 EOC 样本和 40 例 Salah Azaiez 研究所治疗的患者正常卵巢样本中上皮细胞和基质细胞中 MARCKS 的表达。我们比较了正常样本和肿瘤样本中 MARCKS 的表达，并搜索了与临床病理特征的相关性，包括总生存期 (OS)。75%的正常样本上皮 MARCKS 染色呈阳性，而 50%的肿瘤样本呈阳性 (=6.02×10)。相比之下，肿瘤样本中基质 MARCKS 的表达更为频繁 (77%)，而正常样本中则为 22% (=1.41×10)。上皮和基质 IHC MARCKS 状态与预后临床病理特征之间没有相关性。在单变量和多变量分析中，基质 MARCKS 表达与较差的 OS 相关。肿瘤中基质 MARCKS 的过度表达可能有助于癌症相关成纤维细胞的激活，并导致 EOC 的预后不良，这表明 MARCKS 抑制可能成为靶向肿瘤基质的潜在治疗靶点。
