microRNA evaluation of unknown primary lesions in the head and neck

Unknown primary malignancy in the head and neck is not an infrequent diagnosis for patients with metastatic cervical lymph nodes. Although linked with a relatively good prognosis following radiation treatment, widespread radiation is coupled with significant morbidity. Altered microRNA (miRNA) expression has been associated with both cancer progression and metastasis. We sought to determine whether miRNA expression analysis could be used as a diagnostic tool to discover the primary site of malignancy, within the head and neck. We used quantitative real-time PCR to identify miRNA expression profiles of squamous cell carcinoma of the tonsil, base of tongue and post-nasal space, as well as their corresponding metastatic lymph nodes, from 6 patients. Our results revealed that each cancer maintained its expression profile between the primary site and the nodal metastasis (r = 0.82, p < 0.0001). In addition, each anatomical sub-site maintained a distinct miRNA profile between individual patients (r = 0.79, p < 0.0001). Finally, between sub-sites, the miRNA profiles were distinct (p < 0.0001). As proof of principle, our study provides an indication that miRNA expression analysis may be useful to compare the primary lesion and local metastatic disease. This may be clinically relevant to predict the primary site of origin of metastatic disease, when the primary site remains obscure.

Apoptosis as a mediator of hyperplastic recovery in human prostate lesions: cytochemical and immunocytochemical evaluation

The present study was carried out to investigate the occurrence of apoptosis in human prostatic lesions with emphasis on nodular hyperplasia and adenocarcinomas, using cytochemistry and immunocytochemistry. The results showed that apoptosis is a common event on nodular hyperplasia but not in adenocarcinomas. This led to the hypothesis that apoptosis may represent an important factor on the localized recovery response of the hyperplastic acini.

Detection of numerical chromosome anomalies in interphase cells of benign and malignant thyroid lesions using fluorescence in situ hybridization

Benign and malignant thyroid tumors constitute a wide range of neoplasias showing recurrent chromosome abnormalities. In an attempt to characterize specific numerical chromosome abnormalities in thyroid tissues, We present here the findings from a study of archival samples depicted by 10 malignant tumors, 30 benign lesions, and 10 normal thyroid tissues. Fluorescence in situ hybridization was performed on noncultured samples using biotinylated centromere-specific probes for chromosomes 7, 10, and 17. Trisomy or tetrasomy 7 were present in 19 benign and in 7 malignant tumors. Trisomy 10 or 17 were observed in 18 adenomas or goiters and in 9 carcinomas, and monosomy 17 was seen in 2 carcinomas. Our findings suggest that such abnormalities are an in vivo phenomenon and may be important in the neoplastic proliferation of thyroid gland. (C) Elsevier B.V., 2000. All rights reserved.

Expression of TERT in precancerous gastric lesions compared to gastric cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders

The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.

Expression of Ki-67 Antigen and Caspase-3 Protein in Benign Lesions and Esophageal Carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of Staining Methods for Cytologic Diagnosis of Oral Lesions

ObjectiveTo compare the efficacy of Papanicolaou, hematoxylin-eosin (H-E), Leishman and periodic acid-Schiff (PAS) staining for Cytologic diagnosis of oral lesions.Study DesignPatients from the Discipline of Stomatology, Sao Jose dos Campos Dental School, from the wards of Hospital Heliopolis and from the dentistry outpatient clinic of the University Hospital, University of São Paulo Medical School, with the following diseases, were selected: erythematous candidiasis (n = 9), pseudomembranous candidiasis (n = 10), squamous cell carcinoma In = 19), herpes simplex (n = 8), paracoccidioidomycosis In = 8) and pemphigus vulgaris (n = 1).ResultsThe different staining methods were compared regarding the quality of definition of cytoplasmic and nuclear morphologic characteristics and the identification of bacteria, fungi, inflammatory cells and secretions. Papanicolaou and H-E staining were considered better methods. In cases of fungal infections, PAS staining is useful and should be applied as a complementary method.ConclusionWithin the limitations of this study, it can be concluded that the cytologic diagnosis of oral lesions along with different staining methods is a useful tool for oral diagnosis. (Acta Cytol 2008;52:697-701)

Oral distribution of Candida species and presence of oral lesions in Brazilian leprosy patients under multidrug therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diagnosis of inflammatory lesions by high-wavenumber FT-Raman spectroscopy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Caries Infiltration Technique and Fluoride Therapy on Microhardness of Enamel Carious Lesions

Enamel white spot subsurface lesions compromise esthetics and precede cavitation; therefore, they must be halted. The aim of this study was to evaluate the effect of a caries infiltration technique and fluoride therapy on the microhardness of enamel carious lesions. Subsurface carious lesions were produced in 60 bovine specimens with polished enamel surfaces. The specimens were divided into four groups (n=15), according to the treatment used: CON, control immersion in artificial saliva; DF, daily 0.05% fluoride solution; WF, weekly 2% fluoride gel; and IC, resin infiltration (Icon). The specimens were kept in artificial saliva and evaluated for microhardness at five points: baseline, after caries production, after four and eight weeks of treatment, and a final evaluation after being submitted to a new acid challenge. The repeated-measures analysis of variance showed significant differences according to the type of treatment (TREAT; p=0.001) and time of evaluation (EV; p=0.001). The results of the Tukey test were TREAT: CON = 45.18 (+/- 29.17)a, DF = 107.75 (+/- 67.38)b, WF = 83.25 (+/- 51.17)c, and IC = 160.83 (+/- 91.11)d. Analysis of correlation between the TREAT and EV factors showed no significant differences for DF (138.63 +/- 38.94) and IC (160.99 +/- 46.13) after the new acid challenge. The microhardness results in decreasing order after eight weeks were IC > DF > WF > CON. It was concluded that the microhardness of carious lesions increased with the infiltration of resin, while the final microhardness after a new acid challenge was similar for DF and IC.

Comparison of histological and molecular diagnosis of Helicobacter pylori in benign lesions and gastric adenocarcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients

Cutaneous biopsies (n = 94) obtained from 88 patients with American tegumentary leishmaniasis were studied by conventional and immunohistochemical techniques. Specimens were distributed as active lesions of cutaneous leishmaniasis (n = 53) (Group I), cicatricial lesions of cutaneous leishmaniasis (n = 35) (Group II) and suggestive scars of healed mucosal leishmaniasis patients (n = 6) (Group III). In addition, active cutaneous lesions of other etiology (n = 24) (Group C1) and cutaneous scars not related to leishmaniasis (n = 10) (Group C2) were also included in the protocol. Amastigotes in Group I biopsies were detected by routine histopathological exam (30.2%), imprint (28.2%), culture (43.4%), immunofluorescence (41.4%) and immunoperoxidase (58.5%) techniques; and by the five methods together (79.3%). In Group II, 5.7% of cultures were positive. Leishmanial antigen was also seen in the cytoplasm of macrophages and giant cells (cellular pattern), vessel walls (vascular pattern) and dermal nerves (neural pattern). Positive reaction was detected in 49 (92.5%), 20 (57%) and 4 (67%) biopsies of Groups I, II and III, respectively. Antigen persistency in cicatricial tissue may be related to immunoprotection or, on the contrary, to the development of late lesions. We suggest that the cellular, vascular and neural patterns could be applied in the immunodiagnosis of active and cicatricial lesions in which leishmaniasis is suspected.

Leprosy patients: neurotrophic factors and axonal markers in skin lesions

Neurotrofinas são fatores de crescimento com papel fundamental na fisiopatologia neural. Esses mediadores modulam funcionalmente fibras nociceptivas. Mudanças em sua expressão têm sido relacionadas à perda precoce da nocicepção na hanseníase. Este estudo investigou a expressão de NGF, BDNF e NT3 em nervos dérmicos de pacientes hansenianos. A caracterização de fibras nervosas não mielinizadas foi feita por p75NTR e marcadores axonais NF-L e PGP 9.5. Os parâmetros clínicos de dano neural foram avaliados por monofilamentos Semmes-Wenstein. Nossos achados demonstram diminuição de NGF nos pacientes dimorfos em comparação aos controles. Resultados similares foram observados para PGP 9.5 (dimorfos: p<0,001; virchowianos: p<0,05) e NF-L (virchowianos: p<0.05), sugerindo degeneração avançada das terminações nervosas na hanseníase multibacilar. Foi observada correlação positiva entre p75NTR e PGP 9.5, indicando associação entre células de Schwann e axônios em fibras nervosas não mielinizadas. Os resultados indicam que o desequilíbrio na expressão das neurotrofinas pode participar do dano neural periférico.