Department of Pathology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
J Clin Pathol. 2019 Nov;72(11):762-770. doi: 10.1136/jclinpath-2019-205912. Epub 2019 Jun 29.
Knowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs.
Surgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.
Pancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes were (59.3%), (40.7%), (27.8%), (20.4%), (16.7%) and / (each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC, alterations frequent in INT-AC, alterations were exclusive in INT-AC and and alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2.
PB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.
欧洲患者关于壶腹癌(AC)的遗传特征的知识有限。肿瘤标志物在壶腹区域活检中建立恶性诊断的效用尚未完全阐明。我们旨在描述丹麦一系列手术切除的 AC 的临床、病理、免疫组织化学(IHC)和遗传特征。
对 59 例手术切除的 AC 进行了检查,包括(1)临床病理特征,(2)组织学亚型,(3)IMP3、maspin、MUC5AC 和 S100P 的表达,(4)使用基于杂交捕获的平台(Illumina HiSeq2500)进行下一代测序,包括 315 个癌症相关基因和 28 个经常在癌症中重排或改变的基因的内含子。还评估了肿瘤突变负担(TMB)和微卫星不稳定性(MSI)。
胰胆管腺癌(PB-AC)、肠型腺癌(INT-AC)、其他壶腹肿瘤和混合性腺癌分别占 45.8%、23.7%、16.9%和 13.6%。IHC 阳性 AC (评分≥2)的比例为:maspin(94.9%)、IMP3(67.8%)、S100P(39.0%)和 MUC5AC(18.6%)。最常改变的基因是 (59.3%)、 (40.7%)、 (27.8%)、 (20.4%)、 (16.7%)和 / (各 11.1%)。MUC5AC 和 S100P 在 PB-AC 中表达频繁, 改变在 INT-AC 中频繁, 改变在 INT-AC 中是特有的, 改变和 改变在 PB-AC 中。49 例 AC 中有 4 例(8.2%)为 TMB 高/MSI 高,表现为 MLH1 和 PMS2 缺失。
PB-AC 是最常见的 AC 组织学亚型。maspin 和 IMP3 是具有最高敏感性的 IHC 肿瘤标志物。腺癌亚型在多个基因改变方面存在差异,其预测价值仍有待评估。