Toyokawa Gouji, Takada Kazuki, Okamoto Tatsuro, Kawanami Satoshi, Kozuma Yuka, Matsubara Taichi, Haratake Naoki, Takamori Shinkichi, Akamine Takaki, Katsura Masakazu, Yamada Yuichi, Shoji Fumihiro, Baba Shingo, Kamitani Takeshi, Oda Yoshinao, Honda Hiroshi, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ann Thorac Surg. 2017 Jun;103(6):1750-1757. doi: 10.1016/j.athoracsur.2016.12.025. Epub 2017 Mar 24.
Programmed death ligand 1 (PD-L1) was reported to predict the response of immunotherapy; however, the association between PD-L1 expression and radiologic and pathologic features has yet to be elucidated.
In all, 292 patients with resected pathologic stage I adenocarcinoma were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and the radiologic/pathologic invasiveness. Specifically, the radiologic invasiveness and noninvasiveness were determined based on the consolidation/tumor ratio, with a cutoff value of 0.25 by thin-section computed tomography.
Among 292 patients, 47 (16.1%) were positive for PD-L1 expression; the remaining 245 patients (83.9%) were negative for PD-L1 expression. Fisher's exact test demonstrated that PD-L1 expression was significantly associated with a higher consolidation/tumor ratio (p = 0.029) and higher maximum standardized uptake value (p = 0.004). The mean values of consolidation/tumor ratio and maximum standardized uptake in patients with and without PD-L1 expression were 0.845 ± 0.052 and 7.241 ± 0.795, and 0.607 ± 0.023 and 3.60 ± 0.364, respectively (p < 0.001 and p < 0.001, respectively). Among 47 adenocarcinomas harboring PD-L1 expression, the frequencies of PD-L1 expression for consolidation/tumor ratios of 0, 0.1 to 0.25, 0.26 to 0.5, and 0.51 or more were 6.4%, 2.1%, 4.3%, and 87.2%, respectively (p = 0.007). Pathologically, PD-L1 was identified exclusively only in more invasive subtypes, not in less invasive ones, such as atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant ones (p < 0.001).
Expression of PD-L1 was significantly associated with radiologic/pathologic invasive adenocarcinomas. This study provides the first evidence of the radiologic and pathologic invasiveness in resected pathologic stage I adenocarcinoma with PD-L1 expression.
据报道，程序性死亡配体1（PD-L1）可预测免疫治疗的反应；然而，PD-L1表达与放射学及病理学特征之间的关联尚未阐明。
总共对292例接受手术切除的Ⅰ期腺癌患者进行免疫组织化学分析，以检测PD-L1表达，并评估PD-L1表达与放射学/病理学侵袭性之间的关联。具体而言，根据实变/肿瘤比值确定放射学侵袭性和非侵袭性，薄层计算机断层扫描的临界值为0.25。
在292例患者中，47例（16.1%）PD-L1表达呈阳性；其余245例患者（83.9%）PD-L1表达呈阴性。Fisher精确检验表明，PD-L1表达与更高的实变/肿瘤比值（p = 0.029）和更高的最大标准化摄取值（p = 0.004）显著相关。PD-L1表达阳性和阴性患者的实变/肿瘤比值及最大标准化摄取值的平均值分别为0.845±0.052和7.241±0.795，以及0.607±0.023和3.60±0.364（分别为p < 0.001和p < 0.001）。在47例伴有PD-L1表达的腺癌中，实变/肿瘤比值为0、0.1至0.25、0.26至0.5以及0.51或更高时，PD-L1表达的频率分别为6.4%、2.1%、4.3%和87.2%（p = 0.007）。在病理学上，PD-L1仅在侵袭性更强的亚型中被发现，而在侵袭性较弱的亚型中未发现，如非典型腺瘤样增生、原位腺癌、微浸润腺癌和鳞屑样为主型腺癌（p < 0.001）。
PD-L1表达与放射学/病理学侵袭性腺癌显著相关。本研究首次提供了具有PD-L1表达的手术切除Ⅰ期腺癌的放射学和病理学侵袭性证据。
