Discovery proteomics reveals potential protein signature associated with malignant phenotype acquisition in pleomorphic adenoma.

OBJECTIVE: To analyze the proteomic profile of salivary pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) samples and correlate them with the malignant transformation of the PA. MATERIALS AND METHODS: Thirty samples (10 PA, 16 CXPA, and 4 residual PA) were microdissected and submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomic data and protein identification were analyzed through LC-MS/MS spectra using the MaxQuant software. RESULTS: The proteomic analysis identified and quantified a total of 240 proteins in which 135 were found in PA, residual PA, and CXPA. The shared proteins were divided into six subgroups, and the proteins that showed statistically significant differences (p > 0.05) and fold-change > or <2.5 in one subgroup to another subgroup were included. Seven proteins (Apolipoprotein A-I-APOA1, haptoglobin-HP, protein of the synaptonemal complex 1-SYCP1, anion transport protein of band 3-SLC4A1, subunit µ1 of AP-1 complex-AP1M1, beta subunit of hemoglobin-HBB, and dermcidin-DCD) were classified as potential protein signatures, being HP, AP1M1, and HBB with higher abundance for PA to residual PA, APOA1 with higher abundance for PA to CXPA, SLC4A1 with lower abundance in the PA to CXPA, SYCP1with lower abundance for residual PA to CXPA, and DCD with higher abundance in the CXPA with epithelial differentiation to myoepithelial differentiation. CONCLUSIONS: In this work, we demonstrated the comparative proteomic profiling of PA, residual PA, and CXPA, and seven were proposed as protein signatures, some of which may be associated with the malignant phenotype acquisition.

M1 macrophages involved in the pathogenesis of placental chronic villitis of unknown etiology.

INTRODUCTION: Placental villitis is characterized by the presence of inflammatory infiltrate in the placental villous. The objective of this study was to characterize in villitis of unknown etiology (VUE) of the human placentas the subpopulation of M1, important effector cells, and M2 macrophages, immunoregulatory cells. METHODS: Sixteen cases of VUE and three control placentas were examined using immunohistochemistry with antibodies for CD3, CD68, CD11c, and CD163. RESULTS: CD11c appeared predominantly in the inflamed villi when compared to the normal areas (p<.001). These cells corresponded to 41.2% of the macrophage population in the inflamed area and were mainly present inside the villi (36%). With regards to CD163, these cells tended to be in higher amounts in the inflamed villi when compared to CD11c and normal areas. DISCUSSION: We conclude that the almost exclusive presence of M1 macrophages in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The greater amount of M2 in villitis and normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

Secretory carcinoma ex pleomorphic adenoma of the submandibular gland: An immunohistochemical study.

Male patient 60-year-old was referred from another service for expert review of a lesion in the submental region. Pathological review revealed morphological features compatible with salivary gland Secretory carcinoma (SC) in cervical lymph node. The patient underwent removal of the left submandibular gland, left neck dissection and biopsy of left labial commissure region. Anatomopathological examination was observed tumor cells arranged in a solid and ductal/cystic pattern, with abundant droplets of secreted eosinophilic material within these structures and extensive hyalinized area, which presented few cells arranged in a ductal pattern. It was possible to observe the presence of extracapsular extension of neoplastic cells > 6 mm, base on this aspects, Carcinoma ex pleomorphic adenoma was suspected. Immunohistochemical panel showed positivity for mammaglobin, s100, CK7, and adipophilin and negativity for myoepithelial markers and PAS in SC cells. The myoepithelial markers showed positivity for residual cellsin hyalinized area, corresponding to residual Pleomorphic adenoma (PA). In view of these findings, the diagnosis of Secretory carcinoma ex pleomorphic adenoma (SCXPA) was established.

Diagnostic and prognostic value of miRNAs on salivary gland tumors: a systematic review and meta-analysis.

PURPOSE: Different levels of miRNA expression have been described in salivary gland tumors as a potential diagnostic marker and predictor of survival. We systematically reviewed the literature to assess the diagnostic and prognostic value of miRNAs on salivary gland tumors. METHODS: An electronic search was conducted in PubMed, Scopus, Embase, Cochrane, and Web of Science databases. In the meta-analysis, we assumed random-effects model with adjusted hazard ratio (HR) and 95% confidence intervals (95% CI). For prognostic studies, the risk of bias was assessed by Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) and Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for diagnostic studies. RESULTS: Gathered data from 1.131 patients in seven studies demonstrated that different levels of miRNA expression presented diagnostic and prognostic in SGTs. The meta-analysis showed that altered miRNA expression were associated with shortened survival (HR, 2.35, 95% CI, 1.77-3.10, P < .00001). For diagnostic meta-analysis, the overall pooled results for specificity and sensibility were 0.87-0.97 (95% CI, 0.72-1) and 0.68-0.91 (95% CI, 0.51-0.96), respectively. CONCLUSION: MicroRNAs may be useful in prognostication of patients with SGTs; however, the diagnostic value of miRNAs in SGTs is still limited.

Two sides of the same coin: Insights into the myoepithelial cells in carcinoma ex pleomorphic adenoma development.

The myoepithelial cell seems to play an important role as a tumor suppressor in the development of carcinoma ex pleomorphic adenoma. Nevertheless, interesting aspects concerning the other side of the coin, i.e., the contribution of the myoepithelial cell to cell proliferation, were brought to light. Here we highlighted the studies in which myoepithelial cells were presented as tumor suppressors and promoters in the context of PA malignant transformation. In conclusion, even if in a paracrine way, divergent signals can alter the suppressor role of the myoepithelial cell and induce it to compose a microenvironment propitious to the tumor progression of the malignant cells. This would cause myoepithelial cells to succumb and malignant epithelial cells to initiate progression beyond the basal membrane.