Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells.

Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features. Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival. Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23-94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern (p = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS. Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

Cruz-Rico G ，Avilés-Salas A ，Popa-Navarro X ，Lara-Mejía L ，Catalán R ，Sánchez-Reyes R ，López-Sánchez D ，Cabrera-Miranda L ，Aquiles Maldonado-Martínez H ，Samtani-Bassarmal S ，Arrieta O ... -  《-》

PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes.

Miyazawa T ，Marushima H ，Saji H ，Kojima K ，Hoshikawa M ，Takagi M ，Nakamura H ... -  《-》

Clinical significance of ≥ 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.

PD-L1 expression in tumor cells has been associated with the efficacy of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to explore correlations between smoking, genetic profiles, patient outcomes, and PD-L1 expression in NSCLC. PD-L1 expression was evaluated in 241 surgically resected specimens by immunostaining and 50% was set as the cutoff value. Of the 241 tumors analyzed, a PD-L1 tumor proportion score (TPS) of ≥ 50% was detected in 35 cases (14.5%) and a TPS of < 50% in 206 cases (85.5%). A PD-L1 TPS ≥ 50% was significantly associated with smoking and EGFR wild-type status (P < 0.001 and P = 0.039, respectively). Detailed assessment of smoking variables showed that total smoking duration was a predictor of a PD-L1 TPS ≥ 50% (P = 0.001). Univariate and multivariate survival analyses revealed that patients with a PD-L1 TPS ≥ 50% had poorer disease-free and overall survival than those with a PD-L1 TPS < 50% (P = 0.001 and P < 0.001, respectively). The incidence of a PD-L1 TPS ≥ 50% was significantly higher in smoking and EGFR wild-type NSCLC patients, particularly in long-term smokers. A PD-L1 TPS of ≥ 50% was an independent adverse prognostic factor for survival in patients with NSCLC.

Li W ，Song P ，Guo L ，Liu X ，Guo C ，Ying J ，Gao S ... -  《-》

Real-World Prevalence of PD-L1 Expression Among Tumor Samples From Patients With Non-Small-Cell Lung Cancer.

We analyzed the prevalence of non-small-cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 50% and compared the results with the existing data from clinical trials and databases from other countries. The Latin American Cooperative Oncology Group and Grupo Brasileiro de Oncologia Torácica performed a retrospective, cross-sectional study from August 2017 to April 2018. PD-L1 expression was collected from pathology reports from 5 laboratories in Brazil. All tests were sponsored by the pharmaceutical industry on request from the treating medical oncologist. PD-L1 expression was assessed by immunohistochemistry. The variables were summarized as absolute and relative frequencies or the median and interquartile range. Pearson's χ2 test was used to compare the TPS categories stratified by sex, age, and histologic type. All analyses were performed with SAS, version 9.4, and were deemed statistically significant at P < .05. A total of 1512 patients were included in the present study. Their median age was 66 years. Most patients were men (56.02%), and the most common histologic type was adenocarcinoma (58.04%); 109 tumors (11.31%) had EGFR mutations and 34 (3.64%) had ALK gene rearrangements. Overall, 56.54% had a PD-L1 TPS < 1%, 25.63% a TPS of 1% to 49%, and 17.83% a TPS of ≥ 50%. The factors associated with PD-L1 expression were histologic type (with adenocarcinoma samples having a greater proportion of TPS < 1%) and the laboratory that performed the test. The prevalence of high PD-L1 expression among the Brazilian NSCLC samples was lower than previously described in other countries, which could affect the number of patients who might be candidates for immunotherapy alone.

Gelatti ACZ ，Cordeiro de Lima VC ，Freitas H ，Werutsky G ，Gaiger AM ，Klock C ，Viola PP ，Shiang C ，de Macedo MP ，Lopes LF ，De Marchi P ，Albino da Silva EC ，Moura F ，Borges G ，Zaffaroni F ，Nunes Filho PR ，Araujo LH ，Mascarenhas E ，Mathias C ，Barrios C ，Zukin M ... -  《-》

Solid histological component of adenocarcinoma might play an important role in PD-L1 expression of lung adenocarcinoma.

In this study we aimed to clarify the PD-L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD-L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. When PD-L1 expression-positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD-L1 expression, SPA was the only subtype which was statistically significant when both PD-L1 expression-positive was defined by TPS ≥ 1% (p < 0.0001) and TPS ≧ 50% (p < 0.0001). We then considered the solid component. We investigated 279 cases of the other subtype group excluding SPA. The group containing a solid component (≥5%) tended to be PD-L1 expression-positive both when defined by TPS ≥1% (p < 0.0001) and TPS ≧50% (p = 0.0049). The PD-L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.

Miyazawa T ，Morikawa K ，Otsubo K ，Sakai H ，Kimura H ，Chosokabe M ，Furuya N ，Marushima H ，Kojima K ，Mineshita M ，Koike J ，Saji H ... -  《-》