Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case-control study.

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.

Influence of conditioned medium from squamous cell carcinoma of the tongue on lymphoblasts and peripheral blood mononuclear cells.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity and is associated with high morbidity and mortality. Attention has been given to the role of inflammatory cells in carcinogenesis because of the ability of cancer cells to subvert the immune response. However, little is known about how molecules from neoplastic cells interact with lymphoblasts and circulating immune cells. This study aimed to understand the mechanisms by which SCC cells modulate the immune response by analyzing the influence of conditioned medium derived from SCC cell lines on immune cells. METHODS: Lymphoblastic cells (CEM) and peripheral blood mononuclear cells (PBMC) were cultured in a conditioned medium derived from squamous cell carcinoma cells (SCC9 or SCC4) and analyzed for cell viability, CD4/CD8/FOXP3 profile by flow cytometry, and chemokine levels. RESULTS: Conditioned medium derived from SCC4 and SCC9 presented higher concentrations of IL-6 and IL-8 than IL-1ß, IL-10, and IFN-γ. CEM and PBMCs when cultured with conditioned medium derived from SCC4 and SCC9 reduced IL-1ß, IL-8, and IFN-γ concentrations. Conditioned medium from SCC4 increased CD4+ population in both CEM and PBMCs, while in conditioned medium from SCC9 it occurred only in PBMCs. PBMCs when cultured with both conditioned mediums increased CD8+ /FOXP3+ cells. CEM cells when cultured with conditioned medium derived from SCC4 and SCC9 reduced. CONCLUSION: Collectively, our results suggest that the products derived from squamous cell carcinoma on inflammatory cells can promote an immunosuppressed environment by reducing cell viability, changing cytokine expression, and altering the cell immunoprofile.

Oral mucosa lesions in confirmed and non-vaccinated cases for COVID-19: A systematic review.

This systematic review purposed to investigate reports of oral lesions in confirmed COVID-19 patients summarizing clinical characteristics, histological findings, treatment and correlation of oral lesions and COVID-19 severity. Electronic search was conducted on November 2021 using seven databases to identify case reports/series describing lesions in oral mucosa in COVID-19 confirmed cases. A total of 5,179 studies were found, being 39 eligible from 19 countries, totalling 116 cases. It was observed only COVID-19 non-vaccinated cases and no sex or age predilection. The oral lesions presentation was mostly single location (69.8%), commonly in the tongue, lips, and palate, being ulcer the main clinical presentation. According to severity index for COVID-19, the reports were more frequent in patients with mild and moderate symptoms, being 75.8% in acute phase. The oral lesion appearance in post-acute COVID-19 were described after 14 to two months after patient recovery. Histologically, keratinocytes with perinuclear vacuolization, thrombosis and mononuclear inflammatory infiltrate were also described with the presence of the virus in keratinocytes, endothelial cells, and minor salivary glands. In conclusion, health care professionals should consider COVID-19 association when patient present ulcerated oral lesions and mild to moderate symptoms for COVID-19 or had acute-COVID-19.

Central giant cell granulomas of the jaws stromal cells harbour mutations and have osteogenic differentiation capacity, in vivo and in vitro.

BACKGROUND: Central giant cell granulomas (CGCG) of the jaws are osteolytic lesions that may behave aggressively and respond poorly to surgery. Microscopically, in addition to giant cells, there is a mononuclear cell population composed of macrophage/monocytic cells and spindle-shaped cells of mesenchymal origin. Seventy two percent of these tumours harbour mutually exclusive TRPV4, KRAS and FGFR1 mutations. We aimed to assess the mutational status of mononuclear and giant cells and the osteogenic potential of stromal cells in vitro and in vivo. METHODS AND RESULTS: We screened CGCG for signature mutations and used laser-capture microdissection to demonstrate that the mutations are restricted to the mononuclear cells. Additionally, we established CGCG primary cell culture and observed that the cells retained the mutations throughout passages. By flow cytometry, we observed predominance of CD14- CD51- CD61- cells, consistent with the expected profile for stromal cells. Considering the mesenchymal origin of stromal cells, we assessed the osteogenic differentiation potential of CGCG cells in culture by cytochemistry (von Kossa and alizarin red staining), alkaline phosphatase (ALP) activity assay and gene expression of osteogenic markers. CGCG cells presented self-capacity to increase ALP levels in a time-dependent manner and under osteogenic induction presented increasing number of calcium deposits, and overall higher expression of osteocalcin, RUNX2, ALPL and osteopontin than cells without osteogenic induction. A patient-derived xenograft model for CGCG was established, and osteoid material deposition was observed. CONCLUSION: Collectively, the results confirm that the signature mutations are restricted to stromal cells in CGCG, and the in vitro and in vivo results support that these cells have the capacity to differentiate into osteoblasts, in line with the bone formation often observed in the stroma of these lesions.

Patient-derived xenograft models for the study of benign human neoplasms.

Preclinical models are a core feature of translational research, and patient-derived xenograft (PDX) models have increasingly been used with such purpose. PDX involves the transplantation of fresh human tumor samples into immunodeficient mice to overcome immunologic rejection. It is a valuable tool for basic as well as preclinical research, contributing to the establishment of models to characterize the neoplasms to drug screening and to allow the identification of therapeutic targets. The use of these models is justified because they retain the histological and genomic features of the primary tumor. PDX models are well described for malignant neoplasms, for which the advantages are clear and include the development of drug treatments. The establishment of malignant tumors PDX is undeniably important from a medical perspective. However, few studies have used such models for benign neoplasms. The use of PDX for benign neoplasm studies can help to clarify the pathobiology of these diseases, as well as invasion and malignant transformation mechanisms, which from a biological perspective is equally important to the study of malignant tumors. Therefore, the aim of this study is to review the current methodology for PDX model generation and to cover its main applications, focusing on benign neoplasms.

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-ß-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-ß-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-ß-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Characterization of progenitor/stem cell population from human dental socket and their multidifferentiation potential.

Dental stem cells have many applications in medicine, dentistry and stem cell biology in general due to their easy accessibility and low morbidity. A common surgical manoeuvre after a tooth extraction is the dental socket curettage which is necessary to clean the alveolus and favour alveolar bone healing. This procedure can cause very low morbidity compared to bone marrow collection procedures and the collected material is normally discarded. In order to investigate if the tissue obtained by dental socket curettage after a tooth extraction was a feasible alternative source to isolate human stem cells, we isolated and characterized two different stem cell populations based on STRO-1 and CD146 expression. We were able to collect and grow cells from dental socket of vital and non-vital teeth. Both populations were proliferative, clonogenic and expressed STRO-1, CD146, CD90, NG2, PDGFR-ß, which are markers found in stem cells, presented in vitro multiline-differentiation into osteogenic, chondrogenic, and adipogenic tissue, and in vivo transplanted cells formed mineralized tissue. Interestingly, STRO-1+ clonogenic cells presented better multidifferentiation than CD146+ cells. Our results showed that mesenchymal stem cells can be isolated from the tiny tissue collected by dental socket curettage after vital and non-vital tooth extraction and suggest that STRO-1 is an important marker to be used to sort cells with multidifferentiation capacity.

Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma.

BACKGROUND: Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines. MATERIALS AND METHODS: Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib. CONCLUSION: Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.

GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)ß, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.

Can stem cells enhance bone formation in the human edentulous alveolar ridge? A systematic review and meta-analysis.

Several non-biological materials are currently being used to increase the alveolar bone volume to support dental implants. Recently, stem cell therapy has emerged as a promising biological substitute or adjuvant to enhance bone healing. In order to determine if stem cell therapy has enough clinical evidence to bone ridge augmentation in humans, a systematic review and meta-analysis were conducted. Two independent investigators searched the Entrez PubMed, SCOPUS and Web of Science databases for eligible randomized clinical trials that describe stem cell therapies for alveolar bone formation. The included studies were evaluated for risk of bias. A random-effects meta-analysis model was used to evaluate the percentage of bone formation in the selected studies. Heterogeneity was evaluated using the Cochrane Chi 2 and I 2. Nine eligible trials were included. These studies presented an overall unclear risk of bias. A comparison between the lower heterogeneity studies and the long term observational outcomes showed a slight tendency to enhance bone formation. High heterogeneity between the included studies was observed. The lack of outcome standardization made a wide-ranging comparison difficult. The application of stem cells in oral surgery and implantology appears to be promising although more standardized study designs, increased samples and long-term observations are needed to strength the clinical evidence that stem cell therapy is effective for alveolar bone formation.

Monitoring of caries disease by risk assessments and activity

ABSTRACT Dental caries is a non-communicable disease and is considered a public health problem. For diagnosis and correct treatment, the study of risk assessment and caries activity is necessary. The caries risk assessment is a way to formalize the balance and imbalance of predictably disease to diagnose dental caries. Therefore, the caries risk assessment is performed through different evaluation systems. Another parameter of great importance to be studied is the activity of caries, because through it is done the correct treatment decision for the patient. The objective of this article is to inform the reader about: the concepts and caries risk factors; the different caries risk assessment systems described in the literature; and which systems are validated. In addition, this literature review provides for identification and evaluation of risk factors and activity of caries lesions in order to enable greater objectivity in the diagnosis and facilitate the decisions of a successful treatment.

RESUMO A cárie dentária é uma doença não infecciosa e é considerada um problema de saúde pública. Para seu diagnóstico e correto tratamento é necessário a avaliação do risco e da atividade da doença cárie. A avaliação do risco de cárie é uma maneira de formalizar o equilíbrio e desequilíbrio da doença de modo previsível para realizar o diagnóstico da doença presente. Para tanto, a avaliação do risco de cárie é realizada através de diferentes sistemas. Outro parâmetro de grande importância a ser estudado é a atividade da doença cárie, pois através dela é realizada a correta decisão de tratamento para o paciente. Assim, o objetivo do presente artigo foi informar ao leitor: os conceitos e fatores de risco de cárie; os diferentes sistemas de avaliação de risco de cárie descritos na literatura; e quais sistemas são validados. Contudo, esta revisão de literatura proporciona a identificação e avaliação dos fatores de risco e atividade das lesões de cárie afim de possibilitar uma maior objetividade no diagnóstico e facilitar as decisões de um tratamento bem-sucedido.

Terceira dentição: uma visão geral do seu desenvolvimento / Third dentition: an overview of its development

A odontologia moderna, mesmo usando as suas técnicas mais primorosas, na prática, ainda recupera a perda dental com implantes metálicos recobertos por coroas protéticas. Esses métodos, apesar de efetivos, estão longe de repor qualita e quantitativamente todas as estruturas biológicas perdidas. Nesse ínterim, há um empenho coletivo dos cientistas em criar técnicas de desenvolvimento dental que possibilitem a confecção de um dente natural - um biodente - fazendo uso de diferentes populações celulares e técnicas de engenharia de tecidos. Essas pesquisas, apesar de recentes, avançam e prometem revolucionar o futuro da odontologia, uma vez que trazem consigo a perspectiva do desenvolvimento da terceira-dentição em humanos. Apesar de ainda não haverem ensaios clínicos in vivo, já existem trabalhos primorosos revelando diferentes maneiras de se criar um elemento dental por completo em laboratório e de aplicá-lo em modelos animais. Atualmente, usam-se quatro principais técnicas para o desenvolvimento dos biodentes e são justamente sobre elas, suas vantagens, desvantagens e perspectivas de aplicabilidade clínica futura que esse artigo se compromete a fazer uma revisão da literatura.

Even using the best techniches available, modern dentistry still replaces lost with metal implants covered with prosthetic crowns. Although these methods are effective, they are far from reproducing, qualitatively and quantitatively, all the biological structures that were lost. Meanwhile, there is a collective effort of scientists to create techniques that allow a natural tooth (Bio-tooth) to be created, using different cell populations and tissue engineering techniques. Although these researches are recent, they are advancing and promise to revolutionize the future of dentistry, since they offer the possibility of developing the third dentition in humans. In vivo clinical assays are still inexistent but there are that show different ways of making a complete dental element in a laboratory in animal models. Currently, there are four major techniques available to make bio-tooth and this paper makes a literature review to expose them, their advantages, disadvantages and perspective of future applicability in the clinical setting.

FGF-2 is overexpressed in myoepithelial cells of carcinoma ex-pleomorphic adenoma in situ structures.

Increasing emphasis has been placed on the role of myoepithelial cells, the contractile components of secretory glands, in the in situ to invasive carcinoma transition. These cells are placed at the interface between luminal epithelial cells and the stromal compartment, which favors their cross-talk with all other cell types comprising the tumor micro-environment. To obtain some clues about this cross-talk and also to better understand our previous immunoprofile study of myoepithelial cells in salivary gland carcinoma ex-pleomorphic adenoma (CXPA), we investigated FGF-2 expression in CXPA in situ structures as well as in cells cultured under conditions attempting to simulate the cellular interactions of this tumor stage. We have observed by immunohistochemistry that myoepithelial cells of CXPA in situ structures overexpress FGF-2. In addition, our results supported by qPCR and Western blotting, demonstrated that the expression of FGF-2 in the benign myoepithelial cells was in fact increased by stimulation with the conditioned medium from malignant cells. Low molecular weight FGF-2, known to be primarily released from the cells to exert its biological activity through receptors, was the predominant FGF-2 form detected in the benign myoepithelial cells. Specific FGF-2 receptors were found in the malignant epithelial but not in the benign myo-epithelial cells of CXPA, indicating a paracrine role for benign myoepithelial cell-derived FGF-2. Abnormal paracrine myo-epithelial/epithelial cell interactions and also myoepithelial/ stromal cell interactions could favor tumor growth, invasion and metastasis.

FGF-2, TGFbeta-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study.

UNLABELLED: Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. OBJECTIVES: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor beta-1 (TGFbeta-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFbetaR-II and PDGFR-alpha) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. MATERIAL AND METHODS: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. RESULTS: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-alpha had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFbeta-1 and TGFbetaR-II were negative in all samples. CONCLUSIONS: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of these cells through the FGFR-1.

Study of growth factors and receptors in carcinoma ex pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.

FGF-2, TGFâ-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study

Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. OBJECTIVES: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor â-1 (TGFâ-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFâR-II and PDGFR-á) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. MATERIAL AND METHODS: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. RESULTS: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-á had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFâ-1 and TGFâR-II were negative in all samples. CONCLUSIONS: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of ...