This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Mycosis fungoides (MF) is a common, indolent primary cutaneous T-cell lymphoma (CTCL), with rare, more aggressive variants, such as folliculotropic MF (FMF). A minority of the MF cases may undergo large cell transformation (T-MF) associated with poor prognosis. A selection of microRNAs (miRs) contribute to the pathogenesis and progression of classic MF, and may also be useful in differential diagnostics. However, the molecular background of FMF and the mechanisms involved in large cell transformation are obscure. We analyzed the expression of 11 miRs in 9 FMF and 7 T-MF cases. Three miRs, including miR-93-5p, miR-181a and miR-34a were significantly upregulated in both FMF and T-MF. FMF also showed overexpression of miR-155 and miR-223, while miR-181b and miR-326 were overexpressed in T-MF cases compared to controls. These results by identifying a number of differentially expressed microRNAs add further insight into the molecular pathogenesis of folliculotropic MF and large cell transformation of MF.

This is the first study demonstrating the independent prognostic value of mononuclear rings in LUAD cases with brain metastasis. Our results also suggest that the density of tumor-associated ICs in addition to PD-L1 expression of tumor cells and ICs as well as PD-1 expression of ICs may hold relevant information for the appropriate selection of patients who might benefit from anti-PD-L1 or anti-PD-1 therapy.

No abstract

No abstract

Background: Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied. Material and methods: We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and EGFR/KRAS status of the tumors. Results: There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Tumor necrosis was associated with higher PD-L1 expression of TC and PD-1 expression of IC. A negative correlation was observed between lepidic growth pattern and PD-L1 expression of TC and PD-L1/PD-1 expression of IC. EGFR mutation seemed to negatively correlate with PD-1 expression of IC, but this tendency could not be verified when applying corrections for multiple comparisons. No significant effect of the KRAS mutation on any of the studied variables could be established. Conclusion:Here we first demonstrate that the presence of necrosis correlates with higher PD-L1 expression of TC and PD-1 expression of IC in LADC. Further studies are required to determine the predictive value of this observation in LADC patients receiving immunotherapy.

Glioblastomas and brain metastases (BM) of solid tumours are the most common central nervous system neoplasms associated with very unfavourable prognosis. In this study, we report the association of prostate‐specific membrane antigen (PSMA) with various clinical parameters in a large cohort of primary and secondary brain tumours. A tissue microarray containing 371 cases of ascending grades of gliomas pertaining to astrocytic origin and samples of 52 cases of primary lung carcinomas with matching BM with follow‐up time accounting to 10.4 years was evaluated for PSMA expression using immunohistochemistry. In addition, PSMA expression was studied in BM arising from melanomas and breast carcinomas. Neovascular expression of PSMA was evident alongside with high expression in the proliferating microvasculature of glioblastomas when compared to the tumour cell expression. This result correlated with the results obtained from the in silico (cancer genome databases) analyses. In gliomas, only the vascular expression of PSMA associated with poor overall survival but not the tumour cell expression. In the matched primary lung cancers and their BM (n = 52), vascular PSMA expression in primary tumours associated with significantly accelerated metastatic dissemination to the brain with a tendency towards poor overall survival. Taken together, we report that the vascular expression of PSMA in the primary and secondary brain tumours globally associates with the malignant progression and poor outcome of the patients.

Background: Although lung adenocarcinoma (LADC) with sensitizing mutations of the epidermal growth factor receptor (EGFR) is highly sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), in most cases disease progression inevitably occurs. Our aim was to investigate the predictive and prognostic significance of adjusted tumoral EGFR variant allele frequency (EGFR-aVAF) in the above setting.Methods: Eighty-nine Caucasian advanced-stage LADC patients with known exon-specific EGFR mutations undergoing EGFR-TKI treatment were included. The correlations of EGFR-aVAF with clinicopathological variables including progression-free and overall survival (PFS and OS, respectively) were retrospectively analyzed.Results: Of 89 EGFR-mutant LADC patients, 46 (51.7%) had exon 19 deletion, while 41 (46.1%) and 2 (2.2%) patients had exon 21-and exon 18-point mutations, respectively. Tumoral EGFR-aVAF was significantly higher in patients harboring EGFR exon 19 mutations than in those with exon 21-mutant tumors (P<0.001). Notably, patients with EGFR exon 19 mutant tumors demonstrated significantly improved PFS (P=0.003) and OS (P=0.02) compared to patients with exon 21 mutations. Irrespective of specific exon mutations, a statistically significant positive linear correlation was found between EGFR-aVAF of tumoral tissue and PFS (r=0.319; P=0.002). High (≥70%) EGFR-aVAF was an independent predictor of longer PFS [vs. low (<70%) EGFR-aVAF; median PFSs were 52 vs. 26 weeks, respectively; P<0.001]. Additionally, patients with high EGFR-aVAF also had significantly improved OS than those with low EGFR-aVAF (P=0.011).Conclusions: Our study suggests that high (≥70%) EGFR-aVAF of tumoral tissue predicts benefit from Gieszer et al. EGFR-VAF predicts EGFR-TKI efficacy