Anjum Shahzan, Sen Seema, Pushker Neelam, Bajaj Mandeep Singh, Kashyap Seema, Bakhshi Sameer, Chosdol Kunzang, Meel Rachna, Sharma Mehar Chand
Department of Ocular Pathology Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Acta Ophthalmol. 2021 Dec;99(8):e1467-e1473. doi: 10.1111/aos.14812. Epub 2021 Mar 6.
Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features.
A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance.
Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator.
Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.
腺样囊性癌（ACC）是一种侵袭性恶性泪腺肿瘤，预后较差。异常的Notch信号通路已在多种肿瘤中得到研究。然而，关于泪腺ACC中Notch信号通路的研究报道极少。本研究的目的是评估Notch1受体和活化的Notch1（NICD1）在泪腺ACC中的状态，并将其与高危临床病理特征相关联。
本研究纳入了23例经组织病理学证实且接受手术治疗的泪腺ACC患者。通过免疫组织化学方法在福尔马林固定石蜡包埋组织上评估Notch1受体和NICD1的表达。将所得结果与临床病理高危特征及患者生存率相关联。采用Kaplan-Meier生存分析和多因素分析来确定预后意义。
分别在65%和39%的泪腺ACC病例中观察到Notch1受体和NICD1的过表达。在Kaplan-Meier生存分析中，Notch1受体过表达的患者无病生存期缩短。单因素分析显示，男性、骨质侵蚀、神经周围侵犯、实性组织学模式、颅内扩展和晚期肿瘤分期也是预后不良的指标。多因素分析表明，骨质侵蚀是最显著的不良预后指标。
我们的研究表明，Notch1受体过表达在泪腺ACC的生物学行为和侵袭性中起关键作用。骨质侵蚀、实性组织学模式、晚期T分期、神经周围侵犯和颅内扩展是泪腺ACC其他高危临床病理预测指标。
