Estrogen receptor beta (ERβ) expression in different subtypes of malignant pleural mesothelioma

Background: Estrogen receptor beta (ERβ) is a potential target for cancer therapy as a tumor suppressor. Malignant pleural mesothelioma (MPM) is a rare but fatal cancer. This study tries to estimate the incidence of ERβ expression in the various subtypes of MPM tumors. Methods and Materials: In a retrospective study performed at a pulmonary tertiary referral hospital, formalin-fixed paraffin-embedded human tissues of 46 definitive MPM were evaluated for expression of ERβ by immunohistochemistry. Results: ERβ was detected in 14 cases (30.4%) out of the total 46 patients with a mean age of 58.08±11.59 SD, including 33 (71.7%) males. There was no statistically significant difference in patients with positive ERβ staining versus negative cases in age and sex (P >0.05). MPM subtypes included 36 (78.2%) cases of epithelioid mesothelioma, 3 (6.5%) cases of sarcomatoid, 5 (10.8%) cases of biphasic, and 2 (4.3%) cases of desmoplastic subtype. ERβ expression was observed only in epithelioid (11 of total 36 cases) and biphasic (3 of total 5 cases) tumors. There was no significant difference in the incidence of ERβ expression in different subtypes of malignant pleural mesothelioma. Statistical analysis shows a significant difference in the expression of ERβ in the epithelioid subtype (with a more favorable prognosis) versus non-epithelioid subtypes (with poor prognosis, including sarcomatoid, desmoplastic, and biphasic) (P = 0.024). Discussion and Conclusion: Considering the higher proportion of the epithelioid type of MPM with ERβ expression, this highlights the role of ERβ in target therapy of MPM tumor, especially in the epithelioid subtype with a more favorable prognosis. A better understanding of the pathology of mesothelioma will eventually contribute to the development of therapies beyond the existing therapeutic platform.

Livedo of the Forearm in the Aftermath of Forearm Erysipelas

Livedo is an ischemic dermopathy caused by vasculopathies or prothrombotic states, and characterized by the violaceous lace-like mottling of the skin. We report on a patient who developed livedo reticularis – livedo racemosa overlap syndrome as a late sequel of erysipelas, the livedo being restricted to the limb segment affected earlier by erysipelas and devoid of systemic vasculopathy. Though erysipelas and livedo are common disorders, we could not find in the literature reports of an occurrence like that observed in this patient. In this case a favorable prognosis of livedo could be predicted. In a different context, livedo may be the alarming signal of an undiagnosed systemic disease.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

ERAP2 Is Associated With Immune Infiltration and Predicts Favorable Prognosis in SqCLC

BackgroundImmunotherapy has been proven effective among several human cancer types, including Squamous cell lung carcinoma (SqCLC). ERAP2 plays a pivotal role in peptide trimming of many immunological processes. However, the prognostic role of ERAP2 and its relationship with immune cell infiltration in SqCLC remains unclear.MethodsThe differential expression of ERAP2 was identified via GEO and TCGA databases. We calculated the impact of ERAP2 on clinical prognosis using the Kaplan-Meier plotter. TIMER was applied to evaluate the abundance of immune cells infiltration and immune markers. SqCLC tissue microarrays containing 190 patients were constructed, and we performed immunohistochemical staining for ERAP2, CD8, CD47, CD68, and PD-L1 to validate our findings in public data.ResultsIn the GEO SqCLC database, ERAP2 was upregulated in patients with better survival (p=0.001). ERAP2 expression in SqCLC was significantly lower than that of matched normal samples (p<0.05) based on TCGA SqCLC data. Higher expression of ERAP2 was significantly associated with better survival in SqCLC patients from TCGA (p=0.007), KM-plotter (p=0.017), and our tissue microarrays (TMAs) (p=0.026). In univariate and multivariate Cox analysis of SqCLC TMAs, high ERAP2 expression was identified as an independent protective factor for SqCLC patients (Univariate Cox, HR=0.659, range 0.454-0.956, p<0.05. Multivariate Cox, HR=0.578, range 0.385-0.866, p<0.05). In TIMER, ERAP2 was positively correlated with several immune markers (CD274, p=1.27E-04; CD68, p=5.88E-08) and immune infiltrating cells (CD8+ T cell, p=4.09E-03; NK cell, p=1.00E-04). In our cohort, ERAP2 was significantly correlated with CD8+ tumor-infiltrating lymphocytes (TILs) (p=0.0029), and patients with higher ERAP2 expression had a higher percentage of PD-L1 positive patients (p=0.049) and a higher CD8+ TILs level (p=0.036).ConclusionsFor the first time, our study demonstrates that higher expression of ERAP2 is tightly associated with the immuno-supportive microenvironment and can predict a favorable prognosis in SqCLC. Meanwhile, ERAP2 may be a promising immunotherapeutic target for patients with SqCLC.

Experience of successful use of axitinib in therapy of metastatic renal cell carcinoma after immunotargeted therapy

The therapeutic options for clear cell renal cell carcinoma have changed significantly in recent years. Back in 2018, clinical guidelines indicated that the standard of therapy for newly diagnosed metastatic renal cell cancer, regardless of the prognosis, was monotherapy with sunitinib or pazopanib. Accumulation of scientific data and clinical experience has significantly changed approaches to the treatment of this disease – according to current recommendations, pazopanib and sunitinib are considered as a possible option only for patients with a favorable prognosis, while the priority in the treatment of CCRCC for other prognostic groups has shifted towards PD-1/PD-L1 antagonists in combination with ipilimumab or anti-VEGFR-based drugs. At the same time, selecting the optimal regimen for patients who have already received immunotherapy as part of a previous regimen can be very challenging. This publication describes a clinical case of successful therapy with axitinib in a patient with clear cell renal cell carcinoma with a favorable prognosis according to IMDC, with disease progression after using a combination of lenvatinib and pembrolizumab in first-line therapy. The data are presented and discussed in the context of the available evidence base for the use of axitinib in the treatment of metastatic kidney cancer, including after progression of the disease on the background of immunotherapy.