Fabbi Marina, Costa Delfina, Russo Daniela, Arenare Laura, Gaggero Gabriele, Signoriello Simona, Scambia Giovanni, Pisano Carmela, Colombo Nicoletta, Losito Nunzia Simona, Filaci Gilberto, Spina Anna, Califano Daniela, Scognamiglio Giosuè, Gadducci Angiolo, Mezzanzanica Delia, Bagnoli Marina, Ferrini Silvano, Canzonieri Vincenzo, Chiodini Paolo, Perrone Francesco, Pignata Sandro
UO Bioterapie, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
UO Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Diagnostics (Basel). 2022 Aug 31;12(9):2118. doi: 10.3390/diagnostics12092118.
To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan-Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.
为了寻找接受卡铂、紫杉醇和贝伐单抗一线治疗的晚期卵巢癌患者的预后因素，我们研究了癌组织中解整合素和金属蛋白酶17（ADAM17）的表达。ADAM17参与了卵巢癌的发生、发展以及细胞对顺铂的耐药性。我们采用免疫组织化学方法分析了参与MITO16A/MANGO-OV2临床试验的309例卵巢癌患者组织芯片中的ADAM17蛋白表达情况。将染色强度和范围合并为一个半定量视觉分级系统（H评分），通过单因素和多因素Cox回归模型将其与病例的临床病理特征及患者的临床结局相关联。在大多数样本中均检测到ADAM17免疫染色，主要定位于肿瘤细胞，在整个队列中强度各异。根据ADAM17 H评分的最佳临界值绘制的Kaplan-Meier生存曲线显示，ADAM17高表达与无进展生存期（PFS）和总生存期（OS）较差的预后相关。然而，在应用收缩程序调整过拟合风险比估计值后，ADAM17作为预后因素的值消失了。亚组分析表明，ADAM17表达在基线时无残留疾病的病例中可能具有预后相关性，因此可能值得对该患者类别进行进一步研究。
