脊带状Tn抗原与宫颈癌淋巴结状态的关联:一项NRG肿瘤学/GOG研究。
Association of Sialyl Tn antigen with cervical cancer lymph node status: An NRG oncology/GOG study.
发表日期:2023 Feb 22
作者:
Doris M Benbrook, Wei Deng, Michael A Gold, Rajani Rai, Rachel Conrad, Hanke van der Wel, Sanam Husain, Kathleen Moore, Nick Spirtos, Amanda L Jackson, Mae Zakhour, Cara A Mathews, Christopher M West
来源:
GYNECOLOGIC ONCOLOGY
摘要:
对于颈部癌症患者,检测淋巴结转移对于指导治疗决策至关重要,但目前的检测方法准确度有限。我们评估了粘附蛋白(MUC)蛋白质上Tn和STn抗原表达异常与原发肿瘤标本中的淋巴结转移或复发的相关性。我们在全国性临床试验(NCT00460356)中招募了139名进行淋巴结切除术的局部晚期宫颈癌患者进行了手术标本的前瞻性收集。其中,133位患者有原发宫颈肿瘤,67位患者有骨盆淋巴结标本(PLN),28位患者有主动脉旁淋巴结标本(PALN)。固定组织连续切片进行Tn、STn、MUC1或MUC4的免疫组化染色。脱神经酸酶用于验证Tn与STn抗体的特异性。根据临床特征比较染色评分。
超过中位数的原发肿瘤STn表达与阴性PLN状态相关(p值:0.0387;奥斯比比率0.439,95% CI:0.206至0.935)。与主动脉旁淋巴结相比,骨盆淋巴结具有更高的STn,而主要肿瘤具有更高的MUC1,MUC4比主动脉旁淋巴结或骨盆淋巴结高(分别为p=0.017、p=0.011、p=0.016和p<0.001)。Tn和STn表达在原发肿瘤、主动脉旁淋巴结和骨盆淋巴结上相关,Tn和MUC1表达仅在原发肿瘤上相关(Spearman相关系数[r] = 0.301,r = 0.686,r = 0.603和r = 0.249)。原发性宫颈肿瘤中的STn抗原表达是指导治疗决策和参与PLN转移机制的候选生物标志物。版权所有©2023 Elsevier Inc.
Detection of lymph node metastases in cervical cancer patients is important for guiding treatment decisions, however accuracies of current detection methods are limited. We evaluated associations of abnormal glycosylation, represented by Tn and STn antigens on mucin (MUC) proteins, in primary tumor specimens with lymph node metastasis or recurrence of cervical cancer patients.Surgical specimens were prospectively collected from 139 patients with locally-advanced cervical cancer undergoing lymphadenectomy enrolled in a nation-wide clinical trial (NCT00460356). Of these patients, 133 had primary cervix tumor, 67 had pelvic lymph node (PLN) and 28 had para-aortic lymph node (PALN) specimens. Fixed tissue serial sections were immunohistochemically stained for Tn, STn, MUC1 or MUC4. Neuraminidase was used to validate Tn versus STn antibody specificity. Stain scores were compared with clinical characteristics.Primary tumor STn expression above the median was associated with negative PLN status (p-value: 0.0387; odds ratio 0.439, 95% CI: 0.206 to 0.935). PLN had higher STn compared to primary tumor, while primary tumor had higher MUC1 compared to PALN, and MUC4 compared to PALN or PLN (p = 0.017, p = 0.011, p = 0.016 and p < 0.001, respectively). Tn and STn expression correlated in primary tumor, PALN, and PLN, Tn and MUC1 expression correlated in primary tumors only (Spearman correlation coefficient [r] = 0.301, r = 0.686, r = 0.603 and r = 0.249, respectively).STn antigen expression in primary cervical tumors is a candidate biomarker for guiding treatment decisions and for mechanistic involvement in PLN metastases.Copyright © 2023 Elsevier Inc. All rights reserved.