Ricci Costantino, Capizzi Elisa, Giunchi Francesca, Casolari Laura, Gelsomino Francesco, Rihawi Karim, Natali Filippo, Livi Vanina, Trisolini Rocco, Fiorentino Michelangelo, Ardizzoni Andrea
Department of Pathology Maggiore Hospital , Bologna, Italy.
Department of Pathology, Department of Specialistic, Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
Ther Adv Med Oncol. 2020 Nov 30;12:1758835920954802. doi: 10.1177/1758835920954802. eCollection 2020.
Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assessment is mandatory for the single agent pembrolizumab treatment of patients with advanced non-small cell lung cancer (NSCLC). PD-L1 testing has been validated and is currently certified only on formalin-fixed paraffin-embedded materials but not on cytological smears. Unfortunately, a significant proportion of patients, having only cytological material available, cannot be tested for PD-L1 and treated with pembrolizumab. In this study, we aimed to validate PD-L1 IHC on cytological smears prospectively by comparing clone SP263 staining in 150 paired histological samples and cytological smears of NSCLC patients.
We prospectively enrolled 150 consecutive advanced NSCLC patients. The clone SP263 was selected as, in a previous study of our group, it showed higher accuracy compared with clones 28-8 and 22-C3, with good cyto-histological agreement using a cut-off of 50%. For cyto-histological concordance, we calculated the kappa coefficient using two different cut-offs according to the percentage of PD-L1 positive neoplastic cells (<1%, 1-49% and ⩾50%; <50%, ⩾50%).
The overall agreement between histological samples and cytological smears was moderate (kappa = 0.537). However, when the cyto-histological concordance was calculated using the cut-off of 50%, the agreement was good (kappa = 0.740). With the same cut-off, and assuming as gold-standard the results on formalin-fixed paraffin-embedded materials, PD-L1 evaluation on smears showed specificity and negative predictive values of 98.1% and 93.9%, respectively.
Cytological smears can be used in routine clinical practice for PD-L1 assessment with a cut-off of 50%, expanding the potential pool of NSCLC patients as candidates for first-line single agent pembrolizumab therapy.
程序性死亡配体1（PD-L1）免疫组化（IHC）评估对于晚期非小细胞肺癌（NSCLC）患者使用帕博利珠单抗单药治疗是必不可少的。PD-L1检测已得到验证，目前仅在福尔马林固定石蜡包埋材料上获得认证，而在细胞学涂片上未获认证。不幸的是，很大一部分仅有细胞学材料的患者无法进行PD-L1检测并接受帕博利珠单抗治疗。在本研究中，我们旨在通过比较150对NSCLC患者的组织学样本和细胞学涂片上克隆SP263的染色情况，前瞻性地验证细胞学涂片上的PD-L1 IHC。
我们前瞻性地纳入了150例连续的晚期NSCLC患者。选择克隆SP263是因为在我们团队之前的一项研究中，与克隆28-8和22-C3相比，它显示出更高的准确性，使用50%的临界值时具有良好的细胞-组织学一致性。对于细胞-组织学一致性，我们根据PD-L1阳性肿瘤细胞的百分比（<1%、1-49%和⩾50%；<50%、⩾50%）使用两个不同的临界值计算kappa系数。
组织学样本和细胞学涂片之间的总体一致性为中等（kappa = 0.537）。然而，当使用50%的临界值计算细胞-组织学一致性时，一致性良好（kappa = 0.740）。使用相同的临界值，并假设福尔马林固定石蜡包埋材料上的结果为金标准，涂片上的PD-L1评估显示特异性和阴性预测值分别为98.1%和93.9%。
细胞学涂片可用于常规临床实践中的PD-L1评估，临界值为50%，从而扩大了作为一线单药帕博利珠单抗治疗候选者的NSCLC患者潜在群体。
