Histomorphological evaluation, cell proliferation and endothelial immunostaining in oral and maxillofacial myofibroblastic lesions.

BACKGROUND: Myofibroblasts (MF) are mesenchymal cells with features of both fibroblasts and smooth muscle cells. Although these are usually reactive cells, they can lead to myofibroblastic tumors that may share clinical and histomorphological characteristics but with different prognosis. The aim of this study is to perform a histomorphological evaluation as well as to compare and evaluate two different cell proliferation immunomarkers and two endothelial markers in a group of oral and maxillofacial myofibroblastic lesions (MFL). MATERIAL AND METHODS: Cross-sectional and retrospective study. Demographic, clinical, histomorphological and immunohistochemical characteristics of 39 cases of MFL were analyzed. Immunohistochemical reactions were performed with the Ki67, MCM2, CD34 and CD105 antibodies. Kruskal-Wallis test and Spearman correlation analysis were used. RESULTS: Four cases of nodular fasciitis (NF), 18 myofibromas (My), 6 desmoplastic fibromas (DF), 7 inflammatory myofibroblastic tumors (IMT) and 4 myofibroblastic sarcomas (MFS) were studied. There were twenty women (51.2%); the median age was 13 [Q1-Q3: 8-24] years and most cases occurred in the mandible (48.7%). A statistically significant difference with MCM2 immunostaining (p=0.0221) was observed between the MFL; furthermore, a correlation between CD34 and CD105 immunostaining in NF (p <0.0001) and IMT (p=0.0408), between MCM2 and CD34 in IMT (p=0.0362) and between MCM2 and CD105 in MFS (p <0001) were found. CONCLUSIONS: MCM2 immunostaining could assess more clearly the cell growth fraction in MFL. The correlation between MCM2 and CD34 in IMT and between MCM2 and CD105 in MFS are indicative of the high activity of these lesions. These results emphasize the importance of the studied immunohistochemistry markers as possible tools for a better characterization of some of the MFL.

Expression of caveolin-1 in tooth germ, ameloblastoma and ameloblastic carcinoma.

BACKGROUND: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in several biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been associated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1 in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear. MATERIAL AND METHODS: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium (n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) by immunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot. RESULTS: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemical positivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were significantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue, as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1 immunoexpression patterns throughout the stages of TG show its importance during odontogenesis. CONCLUSIONS: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingival epithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immunoexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformation process. However, future studies are needed to clarify and confirm these hypotheses.

Immunoexpression of galectin-3 and its potential relation to hypoxia-inducible factor-1α in ameloblastomas.

In tumor biology, hypoxia triggers signaling pathways that induce transcription of genes related to angiogenesis, metastasis, glucose metabolism and apoptosis. We investigated the expression of hypoxia related proteins, galectin-3 (Gal-3) and hypoxia-inducible factor-1α (HIF-1α), in conventional (CA) and unicystic ameloblastomas (UA). We applied immunohistochemistry for Gal-3 and HIF-1α to 72 cases of ameloblastoma: 59 cases of CA and 13 cases of unicystic UA. Immunoexpression was evaluated semiquantitatively. Gal-3 expression was observed in 40% of the cases: 23/59 CA and 6/13 UA. HIF-1α immunostaining was observed in 55% of cases: 36/59 CA and 4/13 UA. 19 CA and 2 UA were positive for both markers. Immunostaining was evident in the center of the tumor islands, which exhibited squamous metaplasia or cystic degeneration. The expression of Gal-3 and HIF-1α in ameloblastomas could be interpreted as a response to hypoxic stress. Co-expression of both proteins in CA may suggest a potential interaction that participates in the biological behavior of this ameloblastoma variant.

Primordial odontogenic tumor: A systematic review.

BACKGROUND: The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis. AIM: To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features. MATERIAL AND METHODS: An electronic systematic review was performed up to September 2019 in multiple databases. RESULTS: A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for amelogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm. CONCLUSION: POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently.

Adenoid cystic carcinoma with myoepithelial predominance affecting maxilla and maxillary sinus.

Adenoid cystic carcinoma (ACC) represents less than 10% of all salivary gland tumors, rarely occurring centrally in the jaws. Herein we describe the case of a 36-year-old female patient presenting a painless swelling in the right maxilla, resulting in marked facial asymmetry. Intra-orally it was observed a swelling covered by an erythematous and irregular-surfaced mucosa, affecting the gingiva and crossing the midline of the hard palate. Imaging studies showed a mixed radiolucent-radiopaque lesion with ill-defined borders, involving the right side of the maxilla and the maxillary sinus. Incisional biopsy revealed basophilic cribriform tumoral islands and solid sheets of neoplastic cells invading bone trabeculae. Most of the tumoral cells presented myoepithelial characteristics, while few true luminal/epithelial cells were observed. To illustrate the epithelial-myoepithelial pattern, immunohistochemical reactions were performed, as well as double immunohistochemical staining. The diagnosis was intraosseous ACC, which features were discussed as well as the potential differential diagnosis.

Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs.

BACKGROUND: Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the development of this odontogenic neoplasm. MATERIAL AND METHODS: Immunohistochemical assays to determine the presence of proteins hMSH2, hMLH1 and Ki-67 were performed in 80 ameloblastomas (40 solid and 40 unicystic) and five tooth germs. RESULTS: Unicystic ameloblastomas showed higher MMRP expression (hMLH1: 62.5 ± 43.4; hMSH2: 83.3 ± 47.8) than did solid ameloblastomas (hMLH1: 59.4 ± 13.5; hMSH2: 75.8 ± 40.2). Additionally, the cell proliferation index assessed by Ki-67 was inversely proportional to the expression of MMRP. Comparison between tooth germs and ameloblastoma revealed significantly higher expression of hMLH1, hMSH2 and Ki-67 in tooth germs (p=0.02). CONCLUSIONS: The differences of MMRP and Ki-67 immunoexpression between ameloblastomas and tooth germ suggest that alterations in the MMRP mechanisms could participate in the biological behavior of ameloblastomas.