Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear.
Subjects, materials, and methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition.
Results: High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p = .021) and peritoneal recurrence (p = .018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p = .001), OS (p = .001), and peritoneal recurrence (p = .002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p = .013) and diffuse/mixed type gastric cancer (p = .010).
Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer.
Implications for practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.
摘要
背景。间皮素在很多实体肿瘤中会过度表达，近期研究表明，间皮素表达与若干恶性肿瘤的预后不良有关，并且可能在癌症进展过程中起到一定的作用。尽管目前正在进行以间皮素为靶标的免疫疗法的临床试验，但是间皮素表达与胃癌预后之间的相关性尚不明确。
对象、材料和方法。我们对 958 例晚期胃癌患者的癌细胞间皮素表达进行了免疫组织化学评估，并根据染色的强度和程度进行了解释。样本得分为 0 到 2 分，而 2 分则定义为高表达。我们还评估了临床病理因素、总生存期 (OS)、无复发生存期 (RFS) 和初次复发部位，包括腹膜复发。根据美国癌症联合委员会第 7 版进行分期。
结果。在 49.7% 的患者中观察到间皮素高表达，且该间皮素高表达与较高的病理性 T (p = 0.021) 以及腹膜复发 (p = 0.018) 显著相关。多因素生存分析表明，除了分期、淋巴血管浸润和 Lauren 分类之外，间皮素高表达还与不良 RFS (p = 0.001)、OS (p = 0.001) 以及腹膜复发 (p = 0.002) 等因素独立相关。腹膜复发的亚组分析表明，间皮素高表达也是 III 期 (p = 0.013) 和弥漫型/混合型胃癌 (p = 0.010) 的独立预后因素。
结论。间皮素高表达与预后不良相关。此外，间皮素表达、Lauren 分类和分期对腹膜复发而言是意义重大的预测因素。而且，间皮素是 III 期胃癌患者腹膜复发高风险的重要预测因素。
实践意义:本研究表明，间皮素高表达与预后不良相关，并且是 III 期胃癌患者腹膜复发的重要预测因素。本研究为设计弥漫型胃癌患者的抗‐间皮素抗体‐药物偶联物临床试验，从而降低腹膜转移的高风险提供了有效证据。
Keywords: Mesothelin; Peritoneal recurrence; Prediction; Stomach cancer; Survival.
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