Guadagno Elia, de Divitiis Oreste, Solari Domenico, Borrelli Giorgio, Bracale Umberto Marcello, Di Somma Alberto, Cappabianca Paolo, Del Basso De Caro Marialaura
Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
Department of Neurosciences, Reproductive and Odontostomatological Sciences, Division of Neurosurgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
J Exp Clin Cancer Res. 2017 Jul 14;36(1):95. doi: 10.1186/s13046-017-0562-9.
Recurrence is a common feature of craniopharyngiomas, benign tumors that origin from squamous epithelial remnants of Rathke's pouch- arising at any segment of its whole course. There are two histotypes, showing different morphology and clinical behavior: adamantinomatous(adaCP) and papillary (papCP). An univocal strategy of management has not yet been defined, being considered the combination of surgery and radiotherapy the most effective, especially in case of incomplete resection. Therefore, the identification of factors influencing the biological and clinical behaviour is of paramount importance. β-catenin is a cell-cell adhesion protein, whose nuclear localization has been linked to the pathogenesis of adaCP: its nuclear accumulation is associated to the presence of a tumor stem cell subpopulation. The latter is made of cells capable of self-renewal, hence believed to be responsible of recurrence, metastases and resistance to therapy in all tumors. ATM is a kinase activated by autophosphorylation (p-ATM) upon DNA double-strand breaks. It is involved not only in DNA repair, but also in tumor migration and invasiveness. Its expression may have prognostic implications in many neoplastic diseases.
In this study, we measured the immunohistochemical expression of β-catenin, stem cell markers (CD133, CD166), Ki67 and pATMin 45 craniopharyngiomas and correlated it with clinicopathologic features.
Statistical analysis revealed strong correlation of β-catenin with recurrence (p = 0.0039), Ki67 (p = 0.0011, r = 0.4903) and CD166 (p = 0.0002, r = 0.6218). A slight tendency to a higher expression of β-catenin was recorded for adaCP rather than papCP (p = 0.0895).Fisher's exact test showed that CD166 was significantlyrelated with recurrence (p = 0.0040). Furthermore, cytoplasmic pATM was more expressed in adaCPs (p = 0.0470), compared to papCPs that displayed a more evident nuclear signal (p = 0.0313) instead.
Backing upon these data, we could weigh in on the need of identifying β-catenin and CD166 as prognostic markersthat could be useful in predicting thebiologicalbehavior, as recurrence risk incraniopharyngiomas. The final goal is to drew up a prognostic algorithm to be of aid in the planning of an appropriate treatment strategy. Furthermore, our findings demonstrate that pATM could be used as additional distinction-marker between the two histotypes.
复发是颅咽管瘤的一个常见特征，颅咽管瘤是一种起源于拉克氏囊鳞状上皮残余物的良性肿瘤，可在其整个行程的任何节段发生。有两种组织学类型，表现出不同的形态和临床行为：成釉细胞瘤型（adaCP）和乳头型（papCP）。尚未确定一种明确的治疗策略，手术和放疗的联合被认为是最有效的，尤其是在不完全切除的情况下。因此，识别影响生物学和临床行为的因素至关重要。β-连环蛋白是一种细胞间粘附蛋白，其核定位与adaCP的发病机制有关：其核积累与肿瘤干细胞亚群的存在相关。后者由能够自我更新的细胞组成，因此被认为是所有肿瘤复发、转移和耐药的原因。ATM是一种在DNA双链断裂时通过自磷酸化（p-ATM）激活的激酶。它不仅参与DNA修复，还参与肿瘤迁移和侵袭。其表达可能对许多肿瘤性疾病具有预后意义。
在本研究中，我们检测了45例颅咽管瘤中β-连环蛋白、干细胞标志物（CD133、CD166）、Ki67和pATM的免疫组化表达，并将其与临床病理特征相关联。
统计分析显示β-连环蛋白与复发（p = 0.0039）、Ki67（p = 0.0011，r = 0.4903）和CD166（p = 0.0002，r = 0.6218）有强相关性。adaCP中β-连环蛋白的表达略高于papCP（p = 0.0895）。费舍尔精确检验显示CD166与复发显著相关（p = 0.0040）。此外，与显示更明显核信号的papCP相比（p = 0.0313），adaCP中细胞质pATM的表达更高（p = 0.0470）。
基于这些数据，我们可以强调将β-连环蛋白和CD166作为预后标志物的必要性，它们可用于预测颅咽管瘤的生物学行为，如复发风险。最终目标是制定一种预后算法，以帮助规划适当的治疗策略。此外，我们的研究结果表明pATM可作为区分这两种组织学类型的额外标志物。
