Nicoletti Alberto, Vitale Federica, Quero Giuseppe, Paratore Mattia, Fiorillo Claudio, Negri Marcantonio, Carlino Angela, Inzani Frediano, Gasbarrini Antonio, Alfieri Sergio, Zileri Dal Verme Lorenzo
Pancreas Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.
Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.
Cancers (Basel). 2023 Sep 15;15(18):4586. doi: 10.3390/cancers15184586.
(1) Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. The lack of validated disease biomarkers makes timely diagnosis challenging in most cases. Cell membrane and surface proteins play a crucial role in several routes of oncogenesis. The aim of this study was to evaluate the expression of six membrane antigens on PDAC (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Annexin A10 (ANXA10), Glypican-1 (GPC-1)) and their correlation with oncologic outcomes. (2) Methods: Immunohistochemical staining for CA 19.9, MUC1, MUC4, MSLN, ANXA10, and GPC-1 of surgical samples of 50 consecutive patients with PDAC was performed. Antigen expression for tumor, ductal, and acinar tissues was classified according to the histo-score (H-score) by two pathologists. (3) Results: Recurrence rate was 47% and 18 patients (36%) deceased (median follow-up 21.5 months). Immunostaining for CA 19-9 and MUC1 showed a significantly higher expression in the neoplastic tissue compared to non-tumor ductal and acinar tissues ( < 0.001). MUC4, MSLN, ANXA10, and GPC-1 were selectively expressed in the neoplastic tissue ( < 0.001). A CA 19-9 H-score value >270 was independently associated with a worse overall survival ( = 0.05) and disease-free survival ( = 0.05). (4) Conclusions: CA 19-9 and MUC1 are highly expressed in PDAC cells. The histological expression of CA 19-9 may predict prognosis. MUC4, MSLN, ANXA10, and GPC-1 are selectively expressed by neoplastic tissue and may represent a potential histological biomarker of disease.
(1)背景:胰腺导管腺癌(PDAC)是最致命的恶性肿瘤之一。在大多数情况下,由于缺乏经过验证的疾病生物标志物,及时诊断具有挑战性。细胞膜和表面蛋白在多种肿瘤发生途径中起着关键作用。本研究的目的是评估六种膜抗原在PDAC上的表达(CA 19-9、粘蛋白1和4(MUC1、MUC4)、间皮素(MSLN)、膜联蛋白A10(ANXA10)、磷脂酰肌醇蛋白聚糖-1(GPC-1))及其与肿瘤学结局的相关性。(2)方法:对50例连续的PDAC患者手术样本进行CA 19.9、MUC1、MUC4、MSLN、ANXA10和GPC-1的免疫组织化学染色。由两名病理学家根据组织学评分(H评分)对肿瘤、导管和腺泡组织的抗原表达进行分类。(3)结果:复发率为47%,18例患者(36%)死亡(中位随访21.5个月)。与非肿瘤性导管和腺泡组织相比,CA 19-9和MUC1的免疫染色在肿瘤组织中表达明显更高(<0.001)。MUC4、MSLN、ANXA10和GPC-1在肿瘤组织中选择性表达(<0.001)。CA 19-9 H评分值>270与较差的总生存期(=0.05)和无病生存期(=0.05)独立相关。(4)结论:CA 19-9和MUC1在PDAC细胞中高表达。CA 19-9的组织学表达可能预测预后。MUC4、MSLN、ANXA10和GPC-1由肿瘤组织选择性表达,可能代表疾病的潜在组织学生物标志物。