Department of Hospital Pathology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, 07345, Republic of Korea.
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 07345, Republic of Korea.
BMC Cancer. 2020 Mar 14;20(1):216. doi: 10.1186/s12885-020-6673-2.
Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs.
Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed.
A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival.
In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.
包括胰腺、壶腹（ Vater ）和胆总管（ CBD ）在内的壶腹周围癌（ PAC ）具有侵袭性，除 T 分期外，缺乏有用的预后标志物。然而，由于该区域的解剖复杂性，T 分期可能存在偏差。最近，一些与癌症干细胞和上皮-间充质转化（ EMT ）相关的标志物，如八聚体转录因子-4（ Oct4 ）和成纤维细胞生长因子受体 1（ FGFR1 ），已被提议作为其他实体癌的新的有前途的标志物。本研究旨在评估 PAC 中干细胞/EMT 标志物的表达和预后意义。
使用组织微阵列对 1998 年至 2014 年实验室档案中手术切除的 PAC 的福尔马林固定、石蜡包埋组织进行免疫组织化学染色，以评估干细胞/EMT 标志物。记录临床病理参数，并与免疫组织化学结果进行统计学分析。收集和分析生存和复发数据。
共评估了 126 例 PAC 病例。平均年龄为 63 岁，男性 76 例，女性 50 例。年龄小于 74 岁、AOV 癌、较低的 T 和 N 分期、较小的肿瘤大小、无淋巴血管、神经周围浸润和组织学分化良好、肠型、无纤维化、严重炎症与更好的总体生存率显著相关。 FGFR1 以及 CK20 、 CDX2 和 VEGF 的高表达水平与更好的总体生存率显著相关，而其他干细胞标志物则没有相关性。无病生存率的肿瘤复发也观察到类似的发现。
除了其他临床病理参数外，严重纤维化与频繁的肿瘤复发相关，而高 FGFR1 表达与更好的总体生存率相关。需要进一步研究广泛纤维化等组织学变化与 PAC 的 EMT 之间的关系。
