VEGF Immunoexpression in Endometrioid Endometrial Carcinomas.

Vascular endothelial growth factor (VEGF) is the most important stimulator of endometrial tumor angiogenesis, a mechanism that may be a therapeutic target in the context of an incidence and persistent mortality of endometrial endometrial carcinomas (EEC). In this study, VEGF immunoexpression was analyzed for 50 cases of EEC in relation to the histopathological parameters of tumor aggressiveness. High VEGF scores have been associated with the high grade and advanced stage of EEC, but unrelated to the depth of myometrial invasion, the pattern of tumor invasion, or vascular invasion. VEGF may be useful for assessing EEC aggression, but also for tumor angiogenic potential, which recommends it as a possible mark for specific antitumor therapy.

Clinicopathological Prognostic Parameters of Endometrioid Endometrial Carcinomas.

Endometrioid endometrial carcinomas (EEC) are common malignant lesions of the female genital tract, with incidence and risk factors that raise issues to improve histopathological prognostic factors. The study included 50 EEC cases, for which the clinicopathological parameters represented by age, risk factors, tumor grade, histological differences, invasion pattern, tumor stage and association of endometrial hyperplasia were analyzed statistically. The results indicated the predominance of EEC in the 7th decade of life, with associated risk factors (78%), more frequently well differentiated (52%), with no other specifications related to differentiation (NOS, 60%), with irregular invasion pattern (66%) in<50% of the myometrial wall (48%). Irregular pattern, microcystic, elongated, and fragmented (MELF) pattern and myoinvasion associated with vascular invasion (MVI) pattern were significantly associated with high grade and advanced stage tumors. With the exception of EEC-NOS and squamous differentiation, all other tumors were associated with low grade (G1). In this study there was a tendency to associate the age group of 60-69 years with the presence of endometrial hyperplasia and with high grade and advanced stage. Apart from the high grade and advanced stage, in the aggressive profile of the EEC can be included as the clinicopathological parameters the 7th decade of life and the irregular, MELF and MVI invasion patterns.

The analysis of hormonal status and vascular and cell proliferation in endometrioid endometrial adenocarcinomas.

Endometrioid endometrial carcinomas (EECs) are the most common malignancies of the uterus. Hormonal dependence of EEC, in relation to biomolecular mechanisms involved in tumor progression, such as angiogenesis and cell proliferation, are aspects that can contribute to improving the prognosis of patients. We analyzed the immunoexpression of markers addressed to steroid hormone receptors [estrogen receptor (ER), progesterone receptor (PR)], angiogenesis [cluster of differentiation (CD)105∕endoglin] and cell proliferation (Ki-67) in 50 EECs related to the histopathological prognostic criteria of the lesions. In this study, the ER and PR scores were higher in low grade and early stages EEC, the statistical aspects being variable. The CD105 microvessel density and the Ki-67 proliferation index were superior in high grade and advanced stages EEC, the statistical aspects being significant or at the limit of significance. The ER∕PR and CD105∕Ki-67 immunomarker groups indicated a positive linear intragroup relation and a negative linear intergroup relation, suggesting the presence of synergistic and antagonistic molecular mechanisms of tumor endometrial control that can be used to stratify patients for targeted therapy.

The oral mucosa: Epithelial professional phagocytes, lymphatics, telocytes, and false telocytes.

BACKGROUND: The oral mucosa protects the underlying tissue from mechanical damage as well as from the entry of exogenous particles and microorganisms. Telocytes (TCs) are disputed stromal cells featuring peculiarly long and thin processes with uneven calibre known as telopodes, which play a number of roles within the interstitia. The present study aimed to test the key markers recommended for discriminating between TCs and false TCs in samples of normal oral mucosa. METHODS: Archived paraffin-embedded oral mucosa samples were tested by means of immunohistochemistry with the following markers: CD34, D2-40, CD31 and CD68. RESULTS: The epithelial expression of CD68, D2-40 and CD34 was detected. Two subsets of CD34-expressing stromal cells were identified, large cells with telopodial processes, presumably of the hematopoietic lineage, and spindle-shaped TC-like cells. Macrophages and TC-like cells within the lamina propria expressed CD68. The lymphatic endothelia were found to express CD31 and D2-40, but not CD34. Sprouting lymphangiogenesis was demonstrated by the lymphatic endothelial tip cells, which were projecting thin processes within the connective stroma. CONCLUSIONS: The epithelial expression of CD68 suggests the professional phagocytic potential of the oral epithelium. Regarding the TCs and TC-like cells in the oral mucosa they could not be accurately distinguished from other possible cell types, neither on morphological basis (evidence of telopodes) nor by use of panels of markers which include CD34.

Giant abdominal tumor - would you think adrenal?

Adrenal cavernomas are rare benign tumors, and those of giant dimensions are exceptional. Usually, they are symptomless or they induce symptoms and signs due to compression over nearby organs. We present the case of a 68-year-old woman, who complained of abdominal enlargement and abdominal pain in the left part of the abdomen. Imagistic investigations (native and contrast abdominal computed tomography) revealed an inhomogeneous retroperitoneal mass of 210∕182∕200 mm, containing calcifications. Laboratory findings were not relevant, just a slight and non-significant elevation of carcinoembryonic antigen and a slight elevation of C-reactive protein. Diagnosis of cancer of undetermined origin was considered, and surgery was performed. During surgery, a giant encapsulated inhomogeneous tumor of 330 mm, with cystic areas, was removed, without assessing the origin. Primary or secondary tumors (metastasis from breast, intestinal, lung, renal or skin cancer) were taken into account. Only histopathology and immunohistochemistry revealed the diagnosis of adrenal cavernoma. Until this moment, we found only one published article in the medical literature with similar dimensions of an adrenal cavernoma as in our case. Even if rare, hemangioma of the adrenal gland must be considered during the differential diagnosis of an adrenal tumor.

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.

Clinical, statistical, histological and immunohistochemical aspects of periodontal changes in patients with diabetes mellitus.

BACKGROUND: Both diabetes mellitus (DM) and periodontal disease are the most widespread chronic inflammatory diseases that affect a very large number of the population worldwide. AIM: This study's aim was to compare the status of dental hygiene in a group of patients with DM, with patients in the control group, and to histologically analyzing the gum from the subjects with DM. PATIENTS, MATERIALS AND METHODS: The study sample was made up of 53 control subjects and 107 diabetics aged 19-80 years old. We evaluated the following parameters: the plaque index (PI) and the calculus index (CI), according to Simplified Oral Hygiene Index, and the gingival index (GI), according to the Löe & Silness criterion, correlated with glycosylated hemoglobin and the blood sugar levels. RESULTS: For all hygiene indices, the mean values recorded for the control group were significantly lower than the mean values recorded for any sub-category in the diabetic groups. CONCLUSIONS: DM contributes unfavorably to the evolution of periodontal disease. The poor glycemic control and the improper oral hygiene have a negative impact on the health of the periodontium, highlighted by increased scores on PI, CI and GI scales.

The evaluation of the morphological evolution of the tissue integration of dental implants through conventional histology and immunohistochemistry techniques.

Soft peri-implant tissues are important to ensure the integration of a dental implant, and information on their morphophysiology may explain some clinical failures. Through this study, we aim to contribute to a better understanding of the behavior of peri-implant soft tissue, the morphological support being the one that can explain the different clinical situations. Thus, we sought to reconcile clinical, histopathological and immunohistochemical (IHC) aspects of soft peri-implant tissue, in patients who did not show clinical mobility or radiological signs of bone resorption four months after insertion of implants, some of them showing no clinical signs of inflammation. Immunohistochemically, we highlighted the cellular populations participating in the inflammatory process present in the peri-implant mucosa, in the two groups of patients. The IHC identification of these types of cells and the degree to which each of them was represented by the use of monoclonal antibodies can provide additional insight into the local response of peri-implant soft tissue in healing and osseointegration. This helps the clinician to improve the clinical success of dental implant treatment because the soft tissue surrounding the dental implant separates the implant from the oral cavity and makes a biological seal that prevents the development of the peri-implant pathology. Thus, the soft tissue surrounding the dental implants ensures the conditions of osseointegration and hence the long-term survival of an implant.

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%).

Experimental animal model in a histological study of drug-induced gingival overgrowth.

Gingival overgrowth (GO) is a pathology with important aesthetic and functional implications and with a multifactorial pathogenesis. Incriminated etiological factors include antihypertensive, antiepileptic and immunosuppressant medication. We aimed to evaluate the induction of gingival overgrowth on experimental rats, depending on the drug type, dose and duration. In the research conducted by us, the increase in gingival tissue production occurred gradually, depending on the administered medication and the time elapsed after its start. The study conducted shows that experimentally induced gingival overgrowth of the administered drugs is made possible by altering tissue homeostasis through altering the fibrocyte cell populations involved in the tissular turnover as well as those involved in the inflammatory process. A better understanding of the pathogenesis of this undesirable effect may lead to the development of improved management strategies for preventing it, or reducing it through non-surgical methods.

The cadherin switch assessment in the epithelial-mesenchymal transition of urothelial bladder carcinomas.

INTRODUCTION: The epithelial-mesenchymal transition (EMT) process is a complex molecular mechanism that is involved in the acquisition of an aggressive, invasive and metastatic phenotype by carcinomas. The cadherin switch consists in the alteration of E-cadherin and N-cadherin expression and is specific for the EMT process. MATERIALS AND METHODS: This study included 35 cases of primitive urothelial carcinomas investigated in relation with clinicopathological prognostic parameters and expression of E- and N-cadherins in the advancing edge and intratumoral compartments. RESULTS: In both compartments, the immunoexpression of E-cadherin decreased, while that of N-cadherin increased in high grade, deeply invasive, or those cases with lymph node metastases and advanced stages carcinomas, with a negative linear correlation observed between their expression percentage values. In this study, it was observed the presence of cadherin switch in urothelial carcinomas, the variation of the two proteins' immunostaining patterns being higher at the advancing edge. The presence of N-cadherin in intratumoral compartment designated it as actively involved in EMT process. CONCLUSIONS: The analysis of cadherins switch can be used to identify superficial urothelial carcinoma with invasion and metastasis potential.

Clinical, imagistic and histopathological study of chronic apical periodontitis.

Periapical lesions are among the most frequent periodontal pathologies in human teeth, generally called apical periodontitis. Apical periodontitis is a continuation of the endodontic space infection and it is manifested as a response of the host defense against the microbial action. It may determine local inflammation, hard tissue resorption, destruction of other periapical tissues. The preliminary diagnosis of chronic periapical lesions is based on the clinical symptoms and imagistic investigation, which represent a reliable diagnosis instrument, but the histological investigation remains essential for a certain diagnosis. We performed a clinical and histological study of the periapical lesions, evaluating the various clinical and imagistic aspects and we compared them with the results of the histological examination, in order to establish the correspondence between the clinical-imagistic aspects and the morphological ones. The relation between the histological aspects, the clinical signs and imagistic aspects may provide valuable data both for establishing an accurate diagnosis and for adopting the most efficient treatment.

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.

Local cause of gingival overgrowth. Clinical and histological study.

The overgrowth, depending on its extension, has multiple effects on the stomatognathic apparatus: functional disorders (impaired speech), difficulty in chewing and aesthetic problems but can cause significant psychological problems. We proposed this study, motivated by the relative increased frequency of the gum outgrowth, its multifactorial etiopathogeny, but especially from the point of view of the specialist practitioner, by the problems that this pathology raises not only for the functionality of the stomatognathic apparatus but also for the facial esthetics, and especially for future therapeutic attitudes needed to solve the existing pathology at this level. We conducted a clinical study and a histological one. For the clinical study, we selected 74 patients who experienced different degrees of gingival outgrowing associated with fillings, dental caries, fixed prostheses, mobile prostheses, orthodontic apparatus. Thirty gingival fragments from patients with gingival outgrowing were processed by paraffin-embedding histological technique and stained with Hematoxylin-Eosin. The morphological results obtained provide the necessary support for understanding the possibility of developing a therapeutic strategy to prevent or minimize the gum outgrowth by administering antibiotic and anti-inflammatory medications associated with medications, which shall cause the apoptosis of the fibroblasts.

Clinical and histopathological aspects in two cases of ligneous conjunctivitis.

Ligneous conjunctivitis represents a very rare form of chronic membranous conjunctivitis, with unknown etiology; less than 200 cases have been reported in the literature, most of them in infants and children. After 40 years, this condition appears in exceptional circumstances. We present, in this study, two patients (of 55 and 64 years old) with very severe forms of ligneous conjunctivitis, certified by histopathological examination, one of them being previously diagnosed with Lyell's syndrome. The histological examination in ligneous conjunctivitis is important for diagnostic but also to elucidate the etiopathological context. A discontinued hyperplastic conjunctiva with numerous nuclear abnormalities and marked intra- and inter-cellular edema was characteristic for both cases. The epithelium layer presents large area of extension into the connective tissue, in the form of cysts and gland-like structures, or creating deep epithelial lacunas, with goblet cells. The connective subepithelial tissue presents diffuse inflammatory infiltration, with round cells, especially near vessels. Inside the conjunctival tissue, big hyaline areas with rare cellularity are detected. The amorphous deposits containing fibrillar material are also present. At the level of pseudo-membranes, we recorded a massive exudation of fibrin with an inflammatory cellular infiltration, and large areas containing an amorphous eosinophilic hyaline material. The association of ligneous conjunctivitis with Lyell's syndrome in one of our patients suggests its immuno-allergic etiology.

Study of CK18 and GDF5 immunoexpression in oral squamous cell carcinoma and their prognostic value.

Oral cavity cancer remains one of the most common cancers worldwide, with an increased incidence in young adults, although there has been lately a decrease tendency in the incidence of this form of cancer. Lingual localization has a very high mortality and tends to be more aggressive becoming frequently metastatic at the regional lymph nodes. The purpose of this study is to investigate the immunohistochemical expression of cytokeratin 18 (CK18) and the reactivity to GDF5 (CDMP-1), called the morphogenetic protein-1, cartilage-derived, in lingual squamous cell carcinoma and the correlation between the immunoreactivity of this panel of antibodies, and the clinical stage, the degree of differentiation and the invasion pattern. In this regard, we studied the immunohistochemical behavior of these markers in 15 cases of lingual squamous cell carcinoma. In our study, we observed the correlation of CK18 and GDF5 expression with the clinical stage, differentiation degree and invasion pattern, the highest levels of immunoreactivity being recorded in poorly differentiated forms, in high-level invasion patterns and in the most advanced stages. The markers used can become therapeutic targets, which could help increase the quality of life and life expectancy for these patients.

Fulminant evolution in one case of choroidal melanoma - predictive factors for general metastasis.

Comparing with other malignant tumors, uveal melanomas determine tardive general spreading. Even in the absence of local treatment, general metastasis is less than 20%, in the first five years, many factors being involved. This paper present a particular case of choroid melanoma with very unusual and unpredictable evolution of the disease; the high growth of tumor size (in only half year the tumor almost doubled up dimensions), was associated with hepatic metastasis developed in only several months. In our opinion, this case, presenting a very atypical evolution may contribute to increase our knowledge of the mechanisms underlying metastasis and the identification of reliable progression parameters as prognostic markers in primary uveal melanoma. Several histological characteristics and demographic factors have been associated with disease evolution: presence of retinal neovessels and neovascular glaucoma, rapid increasing tumor thickness, scleral invasion, epithelioid cell types with large nucleoli, lymphocytic infiltration, and vascular pattern with networks of loops. Sclera invasion is uncommon in choroid tumors, but it is associated with an unfavorable bad prognosis, giving a great propensity to metastasize and to affect the liver. The median survival following diagnosis of hepatic metastasis is only several months.

The prevalence of the red cell morphology changes in patients with type 2 diabetes mellitus.

Previous studies have shown that hematological alterations are a common finding in patients with diabetes. The aim of our study was to estimate the prevalence of the red cell morphology changes in diabetic patients and their correlation with markers of glycemic control. Thirty patients with type 2 diabetes mellitus were recruited for this study. Patient demographics, relevant concomitant illnesses and medical history were recorded. Anthropometric, biochemical parameters (fasting plasma glucose - FPG, glycated hemoglobin - HbA1c, glomerular filtration rate - GFR) and morphology of blood smear were assessed. Results were compared with the same measurements in 30 subjects without diabetes mellitus. The groups were similar in terms of age and gender but there were statistically significant differences for the recorded parameters in patients of study group and control subjects. Regarding the assessment of FPG, in the study group were recorded averages of 217.70±73.20 mg÷dL compared with controls that compared with controls that had a blood glucose value of 90.03±6.59 mg÷dL. In the study group, mean HbA1c was 7.95±1.99%. For the control group, the mean value of HbA1c was 5.65±0.32%. In the study group, GFR ranged between 47.70 and 118.90 mL÷min.÷1.73 m². For the control group, GFR values were between 88.00 and 130.00 mL÷min.÷1.73 m². In the analysis of blood cytology for the study group, there were changes in the smear type hypochromia, anisocytosis and poikilocyosis (20 patients - 66.66%). In terms of red cell morphology, changes were recorded anulocytes type, red cells in "mark to the target fired" (codocytes), bream (leptocytes), schizocytes, and red cells in "drop" (dacryocytes). We observed a high prevalence of the red cell morphology changes in diabetic patients compared with non-diabetic subjects. Our findings suggest the need of screening for routine hematological tests in type 2 diabetes mellitus.

The novel role of HtrA1 in gingivitis, chronic and aggressive periodontitis.

Proteolytic tissue degradation is a typical phenomenon in inflammatory periodontal diseases. HtrA1 (High temperature requirement A 1) has a serine protease activity and is able to degrade fibronectin whose fragments induce the expression and secretion of several matrix metalloproteinases (MMPs). The aim of this study was to investigate for the first time if HtrA1 has a role in gingivitis and in generalized forms of chronic and aggressive periodontitis. Expression of HtrA1 was investigated in 16 clinically healthy gingiva, 16 gingivitis, 14 generalized chronic periodontitis and 10 generalized aggressive periodontitis by immunohistochemistry and real-time PCR. Statistical comparisons were performed by the Kruskall-Wallis test. Significantly higher levels of HtrA1 mRNA and protein expression were observed in pathological respect to healthy tissues. In particular, we detected an increase of plasma cell HtrA1 immunostaining from gingivitis to chronic and aggressive periodontitis, with the higher intensity in aggressive disease. In addition, we observed the presence of HtrA1 in normal and pathological epithelium, with an increased expression, particularly in its superficial layer, associated with increasingly severe forms of periodontal disease. We can affirm that HtrA1 expression in plasma cells could be correlated with the destruction of pathological periodontal tissue, probably due to its ability to trigger the overproduction of MMPs and to increase the inflammatory mediators TNF-α and IL-1ß by inhibition of TGF-ß. Moreover, epithelial HtrA1 immunostaining suggests a participation of the molecule in the host inflammatory immune responses necessary for the control of periodontal infection.