Highlights
Checkpoint inhibitor therapy affecting PD-L1 as treatment for advanced solid tumors.
Success in trial pembrolizumab therapy in multiresistant metastatic choriocarcinoma.
Long-term remission after pembrolizumab therapy in multiresistant choriocarcinoma.
Only six reported cases, one with comparable follow-up and outcome.
Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.
Background
Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy.
Methods
We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015. Pretreatment serum BChE levels were correlated with clinico-pathological parameters and response to treatment. Uni- and multivariate survival analyses were performed to assess the association between decreased serum BChE levels and progression-free (PFS), cancer-specific (CSS), and overall survival (OS).
Results
A total of 356 patients were eligible for inclusion into the present study. The median (IQR) pretreatment serum BChE level was 6180 (4990–7710) IU/l. Lower serum BChE levels were associated with lower BMI (
p
< 0.001), advanced tumor stage (
p
= 0.04), poor treatment response (
p
= 0.002), the occurrence of disease recurrence (
p
= 0.003), and the risk of death (
p
< 0.001). In uni- and multivariate analyses, low pretreatment serum BChE levels were independently associated with shorter PFS (HR 1.8 [1.2–2.6];
p
= 0.002), CSS (HR 2.2 [1.4–3.5],
p
< 0.001), and OS (HR 2.0 [1.4–2.9];
p
< 0.001).
Conclusions
Low pretreatment serum BChE levels are associated with advanced tumor stage and poor response to treatment, and serve as an independent prognostic biomarker for shorter PFS, CSS, and OS in patients with cervical cancer treated with primary (chemo-)radiation therapy.
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