Purpose: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including ...adenocarcinoma subtypes.Methods: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3.Results: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS).Conclusion: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.
No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to ...unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.
There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior ...to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.
Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC ...remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.
Background
This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose–positron emission tomography/computed ...tomography (FDG-PET/CT) with prognosis in non–small-cell lung cancer (NSCLC).
Methods
We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses.
Results
PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) (P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) (P = 0.0012 and P < 0.0001). Kaplan–Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3.
Conclusion
Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.
Purpose: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma ...(SQ).Methods: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors.Results: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1–3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis.Conclusion: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study.
Background
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.
Methods
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.
Results
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).
Conclusions
The PD‐L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.
When solid component was confirmed even a little (5%≥) in the lung adenocarcinoma patients specimen, PD‐L1 expression tend to positive.
Background
The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand‐1 (PD‐L1), in eight cases each of ...pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital.
Methods
From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD‐L1 status and age, sex, stage, histological type, and prognosis were investigated.
Results
PD‐L1‐positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD‐L1‐positive PSC cases, two showed high PD‐L1 expression in the vimentin‐positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD‐L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD‐L1 staining in the sarcomatoid survived, whereas the other with negative PD‐L1 staining did not.
Conclusion
The present study showed that sarcomatoid carcinoma had a higher PD‐L1 expression compared to non‐small‐cell lung cancer and that both PSC and MPM tended to exhibit PD‐L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.
In malignant pleural mesothelioma (MPM) and pulmonary sarcomatoid carcinoma (PSC), which are thoracic mesenchymal malignant tumors, programed cell death ligand‐1 (PD‐L1) was positive in the vimentin‐positive part or the sarcomatoid area, found to be clinicopathologically significant. In MPM, the effectiveness of immune checkpoint inhibitors (ICIs) has been shown, especially in nonepithelioid type. Our results support the possibility that ICIs will work as well as MPM if PSC is also positive for PD‐L1 and has mesenchymal features such as vimentin‐positive or sarcomatoid compartments.
Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary ...nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.
We are developing a minute tactile sensor having four cantilevers for sensing pressure and shear forces simultaneously and for distributing over a small area to recognize a certain area’s conditions. ...Toward our goal, another important task is to establish, in parallel with the sensor’s fabrication, a computing method that converts measured signals to applied forces. In this paper, we first investigate our sensing mechanism using a centimeter scale mockup of the actual sensor. Then, we formulate the relationship between the applied forces and the sensor outputs by a numerical analysis using a sufficient number of pairings of the forces and outputs. Finally, we examine the potential of the method.
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