Involvement of inflammatory cells in chronic rhinosinusitis with nasal polyps.

Inflammation plays an important role in the pathogenesis of nasal polyps. Understanding the biomolecular action mechanisms of inflammatory elements can contribute to improving the prognosis of these lesions. The study analyzed the distribution and immunohistochemically quantified eosinophils [eosinophil major basic protein (BMK-13)], lymphocytes [cluster of differentiation (CD) 4, CD8, CD20] and plasmocytes (CD138) in both the epithelial and stromal compartment in relation to composite scores, which included specific histopathological parameters for 50 sinonasal polyps. Inflammatory elements predominated at stromal level, the high histological composite scores being frequently associated with increased expression of inflammatory elements. Also, the numerical distribution of inflammatory elements indicated positive linear relations within the groups BMK-13∕CD8 and CD4∕CD20∕CD138, and a negative linear relation between the two groups. This aspect can support the existence of alternative or sequential pathogenic mechanisms involved in the pathogenesis of sinonasal polyps, and the results obtained can be used for a better stratification of patients in order to optimize the therapy.

The prognostic value of CXCR4, MMP-2 and MMP-9 in tongue squamous carcinoma.

Currently, tongue squamous cancer appears to be more frequent, especially among adults under the age of 45. Approximately 50% of these patients are diagnosed late, with clinically detectable metastases; the five-year survival rate of patients with loco-regional metastases is less than 60%. In order to explain this behavior, many investigations have been conducted in recent years, most of them focusing on identification of potential prognostic and therapeutic markers involved in the pathogenesis of tongue cancers. Our research follows the same trend, which aims to study the prognostic implications of immunohistochemical (IHC) expression of markers C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase (MMP)-2 and MMP-9 in 54 cases of tongue squamous carcinoma. The cases were selected from the archives of the Laboratory of Pathology, Emergency County Hospital, Craiova, Romania, from the 2015-2017 period. They were immunohistochemically processed using the labeled Streptavidin-Biotin (LSAB) enzyme detection technique, and as a method of evaluating reactions, the IHC score developed by Remmele & Stegner. Reactivity for the investigated markers was recorded in both primary tumors, parenchymal and stromal, and in lymph node metastases, and also in normal or dysplastic mucosa adjacent to tumor lesions. The maximum tumor reactivity was recorded for CXCR4, followed by MMP-9 and MMP-2. In addition, all of these markers were expressed stronger in the invasion front and especially in the lymph node metastatic forms. This immunoprofile would suggest their implication in loco-regional invasion and dissemination processes, allowing the selection of the most aggressive forms of tongue squamous carcinoma.

Immunohistochemical study of experimentally drug-induced gingival overgrowth.

The increasing frequency of using in the medical practice drugs that have the potential to induce gingival overgrowth (GO) and the existence of many unknown aspects in GO etiopathogenesis have prompted us to carry out this immunohistochemical experimental animal study. We conducted a cell proliferation study by Ki67 immunostaining and a cytokeratin (CK) study using anti-pan-CK AE1∕AE3 and anti-MNF116 antibodies, investigating the differences induced by different classes of drugs that are more frequently involved in the induction of GO. The results of our study indicate that CK AE1∕AE3 plays an important role not only in normal cellular proliferation, but also in hypertrophic tissues, and can be considered a marker of the proliferative process occurring in GO. Immunostaining for the anti-MNF116 antibody was weaker and inconsistent in intensity compared to anti-CK AE1∕AE3 antibody, its staining pattern appearing as diffuse or zonal.

The prognostic value of CXCR4, α-SMA and WASL in upper lip basal cell carcinomas.

Lip cancers account for 10-12% of the total head and neck cancers and, although squamous cell carcinoma is by far the most common lower lip cancer, the basal cell carcinoma (BCC) seems to be more common for the upper lip. Most BCCs have a clinically indolent behavior, but there are also local aggressive and∕or metastatic cases, with the incidence of such cases being estimated at about 1-10% of all cases of BCC. Many of the molecular mechanisms underlying this aggression are still unknown, which is why our study aimed to investigate the potential prognosis of a few markers, such as C-X-C chemokine receptor type 4 (CXCR4), alpha-smooth muscle actin (α-SMA) and Wiskott-Aldrich syndrome like (WASL) in upper lip BCCs. For this purpose, 24 basocellular cancers with this localization have been investigated immunohistochemically, histopathologically belonging to the next varieties: superficial, nodular, micronodular, adenoid cystic, keratotic, sclerodermiform and mixed. Regardless of the histopathological subtype, for all invasive cases we have recorded an increased reactivity of the three markers especially in the invasion front, reactivity also present at the stroma level, especially at the stroma-parenchyma interface. The most intense immunoreactivity was obtained for the micronodular and sclerodermiform subtypes, confirming their biological behavior to be more aggressive than the rest of the investigated strains. All these results confirm the prognostic value of the CXCR4∕α-SMA∕WASL panel in assessing the biological behavior of the upper lip BCC.

The Role Played by Growth Factors TGF-ß1, EGF and FGF7 in the Pathogeny of Oral Pseudoepitheliomatous Hyperplasia.

Pseudoepitheliomatous hyperplasia is an epithelial proliferation that develops in the dermis or lamina propria. It is a lesion associated to another pathology, which appears as a response to a great variety of infectious, neoplastic, inflammatory or traumatic stimuli. The etiopathogeny of this lesion is not clear yet. Therefore, we performed an immunohistochemical study on a group of 20 cases of pseudoepitheliomatous hyperplasia cases associated with inflammatory and neoplastic conditions, by investigating TGFß1 (Beta growth and transformation factor), EGF (Epidermal growth Factor), and FGF7 (Fibroblast growth factor) expressions during in its development. The TGF-ß1 expression was recorded in all the layers of the oral hyperplastic epithelium, going from the basal to the superficial layers, but with a different immunoreactive pattern, according to the region. Our study showed the absence of EGF immunoexpression in the carcinomatous proliferation areas associated to pseudoepitheliomatous hyperplasia and an almost exclusive presence in the hyperplasia lesions associated with inflammatory conditions (in about 30% of the investigated lesions) of a expression varying from poor to moderate for EGF. According to our investigations, we observed the presence of an immunolabeling for FGF7 in 80% of the investigated cases of pseudoepitheliomatous hyperplasia, a maximum of intensity being observed within the cases associated with inflammatory conditions.

Histopathological Study of Oral Pseudoepitheliomatous Hyperplasia.

Pseudoepitheliomatous hyperplasia, also called Heck's disease, is an epithelial, inconstant and conjunctive proliferation that develops as a response to a great variety of stimuli. It is a lesion associated to different diseases, being found in the following etiopathogenic conditions: infectious pathogenic conditions, tumoral pathogenic conditions, inflammatory pathogenic conditions. We studied oral pseudoepitheliomatous hyperplasia for which we performed a histopathological study, on a group of 47 cases of oral pseudoepitheliomatous hyperplasias, where we investigated the following: oral epithelium changes, changes in the underlying lamina propria and associated etiopathogenic conditions. The main changes of the oral epithelium were: elongation of the epithelial apexes (17.02%), acanthosis (100%), dyskeratosis (14.89%), and in the underlying lamina propria: fibrosis (29.78%), inflammatory infiltrate (70.21% and vascular proliferation (10.64%). The most frequent associated etiopathogenic conditions were the infectious ones (55.31%), followed by the tumoral ones (29.79%), on the last place being the inflammatory conditions (14.89%).

Study of some invasiveness markers as pathogenic factors in oral pseudoepitheliomatous hyperplasia.

Pseudoepitheliomatous hyperplasia is a benign reactivated epithelial lesion secondary to another pathology, whose incidence is difficult to establish. There still exist controversies regarding the origin and pathogenesis of these lesions. For this purpose, we performed an immuno-histochemical study upon 20 cases of oral pseudoepitheliomatous hyperplasia associated with inflammatory and neoplastic conditions, investigating a series of markers with a possible pathogenic potential in developing this type of lesions. Thus, the immunoreactivity study for ß-catenin showed the presence of a membrane reactivity in all the stratum spinosum and a predominantly cytoplasmatic reactivity, more rarely a nuclear one, in the cells of the basal stratum cells, especially in the epithelial apices that descend deeply in the chorion. Instead, in the case of vimentin, the reactivity was present only in the epithelial apices, especially in the peripheral cells, in comparison to the central ones, and especially in the cases where the epithelial apices descended deeply in the sublesional chorion. Moreover, we observed that the MMP9 reactivity in pseudoepitheliomatous hyperplasia lesions was present in the cells at the epithelium-chorion interface and especially in the epithelial apices that descend deeply into the chorion, and also in the epithelial chorion and networks. The study for CXCR4 immuno-reactivity showed a good reactivity in almost all layers of this hyperplastic lesion, with a maximum reactivity especially inside the epithelial apices that descend deeply in the sublesional chorion. Such an immunoprofile suggests the ability of the oral epithelial cells to undergo an epithelial mesenchymal transition process, thus acquiring mesenchymal characteristics through which it deeply migrates in the subadjacent chorion and contributes to the formation of epithelial apices in pseudoepitheliomatous hyperplasia. Moreover, the invasive ability of these lesions is also given by the average quantity of matrix metalloproteinases present in the epithelium-chorion interface determined by the activation of CXCR4 receptors at this level.

Immunohistochemical study of the epithelial and stromal components of Warthin's tumor.

Warthin's tumor is a benign monomorphic adenoma with unclear origin with the highest incidence in the sixth and seventh decades. The analysis of tumor markers involved in the pathogenesis of Warthin's tumor can improve the patients' prognosis. This study included 29 cases of Warthin's tumor, which were histopathologically and immunohistochemically examined for different compartments of tumors. For immunohistochemical study, we used as specific markers for epithelial compartment CD117, CEA and AMA, respectively S100 and D2-40 for the stromal compartment. The evaluation of immunoreactions was performed by semiquantitative analysis. The analysis of the CEA, CD117 and AAM immunoexpression allowed observing various patterns of immunostaining for tumor double-layered epithelia, which has the tendency of being similar to that in the normal ductal epithelia. S100 protein positivity similar to Langerhans cells suggests that delayed hypersensitivity can be involved in tumor development. The presence of D2-40 expression in majority of tumor subcapsular vessels, similar to lymph nodes structure, confirms the hypothesis that Warthin's tumor has its origin in regional lymph nodes.

The evaluation of p16 and Ki67 immunoexpression in ameloblastomas.

In this study, we investigated the p16 and Ki67 immunoexpression in 19 ameloblastomas in order to highlight some correlations of these markers with the aggressive variants of tumors. The p16 immunoreaction was present in 90.9% of cases; the highest scores are present in the typical follicular and in the intraluminal unicystic variant, at the opposite pole being the granular cells variant. In these cases, the maximum reaction was observed at the level of the stellated reticulum cells while the lowest reaction was present at the level of cubico-cylindrical peripheral cells of the neoplastic islands. The Ki67 immunoreaction was present in all cases, the highest scores being present in the typical follicular variant, opposite being the ameloblastoma with granular cells cases and that with acanthomatous differentiation type. The immunostained cells were located predominantly at the periphery of the tumoral islands but also in the stellated reticulum cells in the central area. The p16 and Ki67 markers may be useful for distinguishing different types of ameloblastomas in terms of aggressiveness.