状态可能区分胃腺癌发生的两种不同途径。

Status May Differentiate Two Distinct Pathways of Gastric Adenocarcinoma Carcinogenesis.

机构信息

Department of Research and Development, John D. Dingell VAMC, Detroit, MI 48201, USA.

Capital Health Medical Group, 2 Capital Way, Pennington, NJ 08534, USA.

出版信息

Curr Oncol. 2023 Aug 29;30(9):7950-7963. doi: 10.3390/curroncol30090578.

DOI:10.3390/curroncol30090578

PMID:37754493

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10527591/

Abstract

BACKGROUND

We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9.

METHODS

We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP-) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated.

RESULTS

Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP- group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP- with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP- group ( = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups ( = 458) and was significantly lower in the gastric cancer patients ( = 10) and patients with stomach conditions predisposing them to GC ( = 214), compared to controls ( = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS.

CONCLUSION

The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP- phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP- group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival.

摘要

背景

我们基于 HP 状态和肿瘤风险标志物单克隆抗体 Adnab-9 的结合，评估了散发型胃癌的表型。

方法

我们将一个具有极强侵袭性表型的家族性胃癌家系与同一社区内的 HP 阳性（HP+）和阴性（HP-）散发型胃癌（GC）患者进行比较，以确定是否存在类似的表型。这可能有助于发现基因，以了解侵袭性 GC 表型的发病机制，特别是有研究表明与免疫相关基因特征有关，以及评估固有免疫系统（InImS）状态的技术的发展，例如 FERAD 比值（血液铁蛋白：粪便 Adnab-9 结合 OD-背景结合）。对散发组和家族组的肿瘤标本进行 HP 染色，并进行肠上皮化生（IM）检查和 Adnab-9 免疫组化染色。家族性家系标本还检测了 E-钙黏蛋白突变和 APC（腺瘤性结肠息肉病）。评估了生存情况。

结果

在 40 名 GC 患者中，25%为 HP+，其肠上皮化生（IM）和胃萎缩的比例高于 HP-组。家族性胃癌家系的先证者是一位 32 岁的母亲，患有致命性胃癌，她的 13 岁同卵双胞胎幸存下来。1 号双胞胎为 HP-，伴有 IM，而 2 号双胞胎为 HP+。双胞胎均在两年内死于 GC。双胞胎均未发生 APC 或 E-钙黏蛋白突变。HP+散发型 GC 组的总生存率为 2.47 ± 2.58 年，HP-组为 0.57 ± 0.60 年（= 0.01）。家族组的生存率为 0.22 ± 0.24 年。50%的非家族性 GC 患者的固定组织和 2 号双胞胎的胃组织提取物中 Adnab-9 标记呈阳性。分别在六个前瞻性随访患者组（= 458）中确定了 FERAD 比值，胃癌患者（= 10）和有胃癌倾向的胃部疾病患者（= 214）的比值明显低于对照组（= 234 名结直肠癌风险增加但无癌症的患者），这表明固有免疫状态出现异常。

结论

HP+散发型 GC 组似乎在发生癌症之前经历了 HP 感染、IM 和萎缩的序列，而 HP-表型似乎省略了这一序列。家族病例可能代表同时具有这两种特征的亚组，但自然病史与 HP-组非常相似。散发型 GC 可能存在两种不同的局部致癌途径。固有免疫状态也可能与预后有关。识别这些患者将允许进行治疗分层和早期诊断，以改善 GC 的生存。