基底细胞癌患者程序性死亡配体 1 表达与治疗方式数量的关系。
Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities.
机构信息
Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
Department of Dermatology, Stanford University School of Medicine, Redwood City, California2Dermatopathology Service, Department of Pathology, Stanford University School of Medicine, Redwood City, California.
出版信息
JAMA Dermatol. 2017 Apr 1;153(4):285-290. doi: 10.1001/jamadermatol.2016.5062.
IMPORTANCE
Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.
OBJECTIVE
To assess PD-L1 expression in treatment-naive and treated BCCs.
DESIGN, SETTING, AND PARTICIPANTS: This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.
EXPOSURES
Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.
MAIN OUTCOMES AND MEASURES
Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.
RESULTS
Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P = .003) and TILs (47% vs 18%, P = .008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P = .007).
CONCLUSIONS AND RELEVANCE
Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.
重要性
程序性死亡 1（PD-1）抑制剂的反应与几种癌症中的程序性死亡配体 1（PD-L1）表达水平有关，但基底细胞癌（BCC）中 PD-L1 的表达及其临床意义目前尚不清楚。
目的
评估治疗前和治疗后的 BCC 中 PD-L1 的表达。
设计、地点和参与者：这是一项单中心学术三级转诊中心的横断面研究。皮肤科诊所的福尔马林固定 BCC 进行免疫组织化学染色，由皮肤科病理学家和皮肤科医生以盲法进行检查。研究日期为 2014 年 3 月 31 日至 2016 年 6 月 7 日。
暴露
治疗后的 BCC（包括手术后、放疗、全身化疗或局部化疗后复发的 BCC）与未经治疗的 BCC。
主要观察指标和测量方法
肿瘤细胞和肿瘤浸润淋巴细胞（TIL）中 PD-L1 表达的百分比、表达强度以及与治疗方式的关系。
结果
在 62 名患者（男性 43 名，女性 19 名；活检时的平均[标准差]年龄为 61.6[13.7]岁）的 138 例 BCC 中，89.9%（124/138）的肿瘤细胞呈 PD-L1 阳性表达，94.9%（131/138）的 TIL 呈 PD-L1 阳性表达，分别定义为相应细胞群中大于 5%的免疫组织化学染色阳性。在调整诊断时的年龄后，与 60 例未经治疗的 BCC 相比，78 例治疗后 BCC 的 PD-L1 免疫组织化学染色强度在肿瘤细胞（32%比 7%，P=0.003）和 TIL（47%比 18%，P=0.008）中存在显著差异。在调整年龄、性别和 BCC 位置的多变量模型中，肿瘤细胞中 PD-L1 染色强度随不同先前治疗方法的数量而增加（中位数为 0.12；四分位间距，0.03-0.20；P=0.007）。
结论和相关性
我们的数据表明，PD-1 免疫疗法可能对 BCC 有效，包括对先前治疗过的 BCC。这一假设需要在未来的临床试验中进行检验。
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