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Objective Monoclonal antibodies targeting programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) demonstrated promising clinical response. The predictive/prognostic value of PD-1/PD-L1 immunohistochemistry (IHC) has been evaluated in many cancer types. However, the prognostic value of PD-1/PD-L1 IHC has not been evaluated in endometrial cancer. Methods We conducted a retrospective study to quantify the IHC CD8, PD-1, and PD-L1 expressions in immune cells at center of tumor (CT), invasive margin (IM), and/or tumor cell in 183 primary endometrial cancer samples from a single cohort, followed by their reciprocal combinations, including compartmental differences, and correlated them with overall survival (OS) and progression-free survival (PFS). Results In repeated Cox multivariable models adjusted by clinicoimmunopathologic factors, high CT-PD-L1 was an independent adverse prognostic factor for PFS in all patients and in the microsatellite-stable subgroup. Immune marker ratios revealed independently shorter PFS for high CT-PD-L1/CT-CD8 and CT-PD-L1/CT-PD-1 ratios. Classification of endometrial cancer into four groups based on CT-CD8 and CT-PD-L1 revealed significantly different survival among groups. Conclusions The high PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent poor prognostic factors for PFS in endometrial cancer, providing insights into the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Abstract: Beta amyloid plaques, neurofibrillary tangles, and impaired glucose metabolism are among the most prevalent pathological characteristics of Alzheimer''s disease (AD). However, separate visualization of these three AD-related pathologies in living humans has not been conducted. Here, we show that positron emission tomography (PET) imaging using the three radiotracers (11)C-Pittsburgh compound B (PIB), 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (FDDNP), and 2-[18F]fluoro-2-deoxy-d-glucose (FDG), in the same subjects, with and without AD, can provide valuable information on the pathological patterns of the distribution of tracers for amyloid plaque, neurofibrillary tangle, and glucose hypometabolism in AD. Voxel-based analysis of PIB-PET in patients with AD compared with normal control subjects showed that patients with AD have highly significant PIB retention in brain regions known to have high amyloid plaque deposition (e.g., frontal, parietal, temporal, and posterior cingulate/precuneus cortices). In contrast, voxel-based analysis of FDDNP-PET showed significantly high FDDNP binding in some brain regions known to have high tangle accumulation in patients with AD compared with age-matched normal subjects (e.g., entorhinal cortex, inferior temporal gyrus, and secondary visual cortex). In addition, because FDDNP binds both plaques and tangles but PIB binds plaques specifically, we examined subtracted PET data (FDDNP minus PIB) acquired from the same patients with AD using an SPM analysis. We found that the hippocampal formation was the most significant brain region in the voxel mapping of FDDNP minus PIB in the same patients with AD. Voxel-based analysis of FDG-PET in the same subjects revealed that brain regions with glucose hypometabolism in patients with AD overlap with regions of high PIB binding. In conclusion, PET imaging using these three radiotracers in the same subjects may contribute toward developing and testing disease-modifying drugs targeting amyloid pathology, tau pathology, and/or energy metabolism. [Copyright &y& Elsevier]

Abstract: Recently developed positron emission tomography (PET) tracers, such as PIB and FDDNP, help to visualize amyloid plaques and neurofibrillary tangles in living subjects. FDDNP binds to both amyloid plaques and tangles, whereas PIB selectively labels amyloid plaques. Therefore, it will be interesting to see a direct comparison of the regional binding of the two radiotracers for plaques (PIB) and plaques and tangles (FDDNP) using multitracer PET imaging for both PIB and FDDNP in the same subjects with and without Alzheimer''s disease. Here we report that multitracer PET images of PIB and FDDNP in the same Alzheimer subjects show negligible PIB but strong FDDNP binding in the medial temporal cortex (hippocampus, amygdala, and parahippocampal gyrus), whereas there are significant quantities of both PIB and FDDNP binding in neocortical areas. These results suggest that tangles rather than amyloid plaques are the dominant pathology in the medial temporal cortex of living Alzheimer patients. In nondemented elderly normal subjects, PIB binding shows a significant increase in the posterior cingulate cortex compared with other brain regions, whereas in the same normal subjects we found significant FDDNP binding in the medial temporal cortex. Interestingly, the medial temporal FDDNP uptake values in normal elderly subjects were inversely correlated with long delay recall scores in the California Verbal Learning Test, a measure of episodic memory performance. We conclude that multitracer PET imaging of amyloid plaques and tangles using FDDNP and PIB in both nondemented and demented subjects provides important insight into these complicated pathological processes in living subjects. [Copyright &y& Elsevier]