General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy.
Division of Surgical Pathology, University-Hospital of Pisa, Pisa 56124, Italy.
World J Gastroenterol. 2020 Nov 21;26(43):6822-6836. doi: 10.3748/wjg.v26.i43.6822.
Ampullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into three important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent. However, they respond differently to chemotherapy and have different prognostic outcomes. The SC are often difficult to identify with conventional histology alone. The clinical outcome of all three remains unclear, particularly for MT.
To identify two main subtypes of AACs, using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20.
Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2, CK7 and CK 20. An IHC score was obtained for each marker by counting the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained by summation of the IHC scores of each marker. The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype, obtaining only two AACs subtypes. The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.
Histological parameters defined the AACs subtypes as follows: 15% INT, 45% PB and 40% MT. Using IHC expression and the GS, 75% and 25% of MT samples were assigned to either the INT or the PB group. The mean value of the GS was 9.5 (range 4-16). All INT samples had a GS above the average, distinct from the PB samples which had a GS score significantly below the average ( = 0.0011). The INT samples were identified by high expression of CDX2 and CK20, whereas PB samples exhibited high expression of CK7 and no expression of CK20 ( = 0.0008). The INT group had a statistically significant higher overall survival than in the PB group (85.7 mo 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; = 0.0152).
The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes, which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.
壶腹腺癌（AAC）是异质性肿瘤，目前分为三个重要亚类（SC）：肠型（INT）、胰胆管型（PB）和混合型（MT）。不同的亚组具有相似的临床表现，均采用胰十二指肠切除术进行治疗。然而，它们对化疗的反应不同，预后结果也不同。SC 通常仅通过常规组织学难以识别。所有三种类型的临床结果仍然不清楚，特别是对于 MT。
使用基于 CDX2、CK7 和 CK20 的免疫组化（IHC）评分来确定 AAC 的两种主要亚型。
对 21 例接受 AAC 切除术的患者的组织样本进行 HE 组织学和 CDX2、CK7 和 CK20 的免疫组化表达分类。通过计数阳性细胞（0 = 无染色细胞；1 < 25%；2 < 50%和 3 > 50%）及其强度（1 = 弱；2 = 中等和 3 = 强），为每个标志物获得 IHC 评分。然后，通过对每个标志物的 IHC 评分求和获得总体评分（GS）。根据主要免疫表型，MT 肿瘤被分为 INT 或 PB 组，仅得到两种 AAC 亚型。通过 Kaplan-Meier 方法获得 INT 和 PB 患者的总生存率。
组织学参数将 AAC 亚型定义为：15%为 INT，45%为 PB，40%为 MT。使用 IHC 表达和 GS，75%和 25%的 MT 样本被分配到 INT 或 PB 组。GS 的平均值为 9.5（范围 4-16）。所有 INT 样本的 GS 均高于平均值，与 PB 样本明显不同，PB 样本的 GS 评分明显低于平均值（= 0.0011）。INT 样本的特征是 CK20 和 CDX2 高表达，而 PB 样本则表现为 CK7 高表达且 CK20 不表达（= 0.0008）。INT 组的总生存率明显高于 PB 组（85.7 个月 20.3 个月，HR：8.39；95%CI：1.38 至 18.90；= 0.0152）。
组织病理学和分子标准的结合使 AAC 能够分为两种具有临床意义的组织分子表型，这似乎代表了具有潜在显著变化的不同疾病，可能对当前的治疗策略产生影响。
