Background

Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.

Methods

The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.

Results

Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).

Conclusion

PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

中文翻译：

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原发部位不明的癌症中的 PD-L1 表达和微卫星不稳定性 (MSI)

背景

原发部位不明的癌症 (CUP) 是一组起源尚不清楚的异质性肿瘤。临床结果可能会受到其微环境中的监管过程的影响。微卫星不稳定性 (MSI) 是癌症免疫治疗的预测生物标志物，其状态以及与 PD-L1 表达的共现性评估很少。我们的目的是评估 CUP 中 PD-L1 的表达和 MSI 状态及其与临床病理特征的可能关联。

方法

通过免疫组织化学评估组合阳性评分 (CPS) PD-L1 表达。使用六重标记组通过聚合酶链反应和随后的片段分析来评估 MSI 状态。

结果

在这 166 例病例中，120 例 MSI 分析得出结论，其中 2 例 MSI 阳性（1.6%）。 109例可行病例中，18.3%的PD-L1表达呈阳性。 PD-L1 表达与非内脏转移和淋巴结转移显着相关。中位总生存期 (mOS) 为 3.7 (95% CI 1.6–5.8) 个月，与不表达 PD-L1 的患者相比，表达 PD-L1 的患者获得了更好的 mOS（18.7 个月与 3.0 个月，p值：< .001）。在多变量分析中，ECOG-PS 等于或大于 2 和 PD-L1 表达是独立的预后因素（分别为 2.37 和 0.42）。

结论

PD-L1 在 CUP 患者的子集 (1/5) 中表达，并与总体生存率改善相关，而 MSI 是一种罕见事件。需要更好地探索肿瘤微环境以及免疫疗法的作用，以改变如此糟糕的临床结果。