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)

Fluorescence spectroscopy for the detection of tongue carcinoma - validation in an animal model

The efficacy of fluorescence spectroscopy to detect squamous cell carcinoma is evaluated in an animal model following laser excitation at 442 and 532 nm. Lesions are chemically induced with a topical DMBA application at the left lateral tongue of Golden Syrian hamsters. The animals are investigated every 2 weeks after the 4th week of induction until a total of 26 weeks. The right lateral tongue of each animal is considered as a control site (normal contralateral tissue) and the induced lesions are analyzed as a set of points covering the entire clinically detectable area. Based on fluorescence spectral differences, four indices are determined to discriminate normal and carcinoma tissues, based on intraspectral analysis. The spectral data are also analyzed using a multivariate data analysis and the results are compared with histology as the diagnostic gold standard. The best result achieved is for blue excitation using the KNN (K-nearest neighbor, a interspectral analysis) algorithm with a sensitivity of 95.7% and a specificity of 91.6%. These high indices indicate that fluorescence spectroscopy may constitute a fast noninvasive auxiliary tool for diagnostic of cancer within the oral cavity. (C) 2008 Society of Photo-Optical Instrumentation Engineers.

Implications of genetic variability of Trypanosoma cruzi for the pathogenesis of Chagas disease

O Trypanosoma cruzi, agente etiológico da doença de Chagas, apresenta elevado grau de variabilidade genética intra-específica, com possíveis implicações na forma clínica da doença, como o desenvolvimento de cardiopatia, do megaesôfago e do megacólon de forma isolada ou em associação. Este tropismo tecidual envolvido na patogênese da doença não está totalmente esclarecido. Assim, nesta revisão são abordados alguns aspectos referentes à diversidade genética dos parasitas isolados, às formas clínicas da doença de Chagas, ao processo de infecção do parasita na célula hospedeira e resposta imune. Outros aspectos também são enfocados, como os fatores imunossupressivos liberados pelo parasita que atuam na regulação das respostas imunes, a inibição da apoptose da célula hospedeira, assim como da patogênese do megaesôfago chagásico que pode estar relacionada à interação hospedeiro- parasita e sua associação com risco aumentado para o desenvolvimento do carcinoma epidermóide do esôfago. Porém, apesar dos avanços no entendimento desta doença, ainda não é possível estabelecer o verdadeiro perfil da variabilidade genética do parasita com a forma clínica da doença de Chagas.

Terapêutica no carcinoma de células escamosas cutâneo em gatos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparative genomic hybridization analysis detects frequent over-representation of DNA sequences at 3q, 7p, and 8q in head and neck carcinomas

Comparative genomic hybridization (CGH) was used to identify chromosomal imbalances in 19 samples of squamous cell carcinoma of the head and neck (HNSCC). The chromosome arms most often or er-represented were 3q (48%), 8q (42%), and 7p (32%); in many cases, these changes were observed at high copy number. Other commonly over-represented sites were 1q, 2q, 6p, 6q, and 18q. The most frequently under-represented segments were 3p and 22q. Loss of heterozygosity of two polymorphic microsatellite loci from chromosome 22 was observed in two tongue tumors, in agreement with the CGH analysis. Gains of 1q and 2q material were detected in patients exhibiting a clinical history of recurrence and/or metastasis followed by terminal disease. This association suggests that gain of 1q and 2q map be a new marker of head and neck tumors with a refractory clinical response. (C) 2000 Elsevier B.V. All rights reserved.

Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy in patients with stage IB carcinoma of the cervix

Objectives. This study was undertaken to evaluate the expression of p53, Ki-67, and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in patients with stage IB squamous cell carcinoma of the cervix, as an attempt to use these proteins as possible markers for residual tumor in cervical cancer.Methods. Thirty patients with stage IB squamous cell carcinoma of the cervix were submitted to radical hysterectomy (study group), and thirty patients with uterine myoma were submitted to vaginal hysterectomy (control group) and were prospectively studied from November 2001 to September 2002. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological examination showed tumor involvement were excluded from the study.Results. Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal margins of radical hysterectomy in patients with cervical carcinoma compared to the vaginal margins of control patients. This association was demonstrated for p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no difference in p53, Ki-67, and CD31 expression between the proximal and distal regions of the vaginal margins in patients with carcinoma of the cervix.Conclusion. The expressions of p53, Ki-67, and CD31 were significantly higher in both the histologically positive (cervical tumor) and negative (vaginal margins) tissues of patients who had undergone radical hysterectomy for cervical cancer compared to the benign control tissues. (C) 2004 Elsevier B.V. All rights reserved.

Angiogenesis and skin carcinomas with skull base invasion: A case-control study

Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome.Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs.Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = 133).Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. (C) 2004 Wiley Periodicals, Inc.

COORDINATE EXPRESSION OF CYTOKERATIN-7 AND CYTOKERATIN-20 DEFINES UNIQUE SUBSETS OF CARCINOMAS

We tested the hypothesis that the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) could distinguish among carcinomas arising from different primary sites. A total of 384 cases of carcinomas primary to various organs, as well as 16 cases of malignant mesothelioma, were evaluated using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase technique. The subset of tumors strongly expressing both CK 7 and CK 20 included virtually all bladder transitional cell carcinomas and the majority of pancreatic adenocarcinomas; the tumors negative for both CK 7 and CK 20 were largely restricted to hepatocellular, prostate, and renal cell carcinomas in addition to squamous cell and neuroendocrine carcinomas of lung. The CK 7-/CK 20+ immunophenotype, however, was highly characteristic of adenocarcinomas of colorectal origin, whereas CK 7+/CK 20- immunophenotype was typically seen in the vast majority of carcinomas arising from other sites, including ovary, endometrium, breast, and lung, as well as malignant mesothelioma. Gastric carcinomas were the most heterogeneous subgroup with respect to CK 7/CK 20 immunophenotype. In the subset of mucinous tumors, striking immunophenotypic differences were noted among those primary to the breast (CK 7+/CK 20-), gastrointestinal tract (CK 7-/CK 20+), and ovary (CK 7+/CK 20+). In all cases investigated, this CK immunophenotype was invariant in metastatic vs. primary tumors. It is concluded that, in the appropriate clinical setting, the CK 7/CK 20 immunophenotype of carcinomas is a valuable diagnostic marker in the determination of primary site of origin.

Clinicopathological features influencing pelvic lymph node metastasis and vaginal and parametrial involvement in patients with carcinoma of the cervix

Purpose: This study was undertaken to evaluate clinical and pathologic findings that predicted pelvic lymph node metastasis and parametrial and vaginal involvement in patients with stage IB carcinoma of the cervix. Methods: 71 patients with diagnosis of stage IB (FIGO) cervical cancer were prospectively studied from December 1997 to August 2002. The patient's age, clinical stage (IB1 or IB2), histological classification, grade of differentiation, tumor volume, and lymphatic vascular space invasion (LVSI) were evaluated. Statistical methods included chi(2) test and Fisher's exact test to evaluate significant differences between the groups. The level of significance was set at p < 0.05. Results: the clinical stage was IB1 in 51 patients (71.8%) and IB2 in 20 patients (28.2%). The histological classification identified squamous cell carcinoma in 60 patients (84.5%) and adenocarcinoma in 11 patients (15.5%). The average tumoral volume was 22.8 &PLUSMN; 8 24.3 cm(3) (0.3-140.0 cm(3)). The tumor was well differentiated (G1) in 8 (11.3%), moderately differentiated (G2) in 40 (56.3%) and poorly differentiated in 23 (32.4%) of the cases. The presence of LVSI was detected in 14 patients (19.7%) and was associated with pelvic lymph node metastasis and vaginal and parametrial involvement (p = 0.002, p = 0.001 and p < 0.001; respectively). The average number of positive pelvic lymph nodes was significantly higher in the patients with LVSI compared with patients without LVSI (2.47 +/- 2.8 vs. 0.33 +/- 0.74; p = 0.001). There was no association of age, clinical stage, histological classification, grade of differentiation or tumor volume with pelvic lymph node metastasis and vaginal and parametrial involvement. Conclusion: the presence of LVSI is significantly associated with pelvic lymph node metastasis and vaginal and parametrial involvement in patients with stage IB cervical carcinoma. Copyright (C) 2005 S. Karger AG, Basel.

Placental glutathione S-transferase correlates with cellular proliferation during rat tonguie carcinogenesis induced by 4-nitroquinoline 1-oxide

Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a crucial role during carcinogenesis, the goal of this study was to investigate the expression of placental GST, called GST-P, and proliferating cellular nuclear antigen (PCNA) by means of immunohistochemistry during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). This is a useful model for studying oral squamous cell carcinoma phase by phase. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. GST-P positive foci were detected in non-neoplastic oral cells at 4 weeks of 4NQO administration. In the same way, GST-P positive cells were detected in pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks-treatment, respectively. None of the control animals expressed GST-P positive cells. Regarding cellular proliferation, PCNA positive nuclei were higher at 12 and 20 weeks following 4NQO exposure (p < 0.05) when compared to negative control. These results suggest that the expression of GST-P is correlated with cellular proliferation, in which GST-P is associated with risk and progression of oral cancer, whereas PCNA is closely involved during neoplastic conversion. (c) 2007 Published by Elsevier GmbH.

Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma

Patients with chagasic achalasia (megaesophagus) are liable to have an additional 1.7-20% possibility of developing esophageal squamous cell carcinoma (ESCC). We applied a fluorescence in situ hybridization technique in 20 such patients and found aneuploidies of chromosomes 7, 11, and 17 in 60% (12 of 20 specimens) and deletion of the TP53 gene in 54.5% (6 of 11 specimens; it was only possible to obtain data by FISH technique from 11 of the 20 achalasia patients). The main aneuploidies detected were chromosome 7 monosomy or trisomy (35%) in mid-third megaesophagus cases, and chromosome 17 monosomy or trisomy (25%) in distal-third cases. TP53 gene deletion was more frequent in mid-third (62.5%) than in distal-third megaesophagus cases (40%). In chagasic megaesophagus, no amplification of the cyclin D1 gene (CCND1) was observed. Comparing chagasic megaesophagus to ESCC, we found a higher frequency of aneuploidies in all 10 tumors. The main alterations were trisomy or tetrasomy of chromosomes 17 (90%), 11 (70%), and 7 (70%). Amplification of CCND1 was evidenced as a cluster in 70% of the tumors (22-99% of nuclei), while TP53 gene deletion occurred in 100%. To our knowledge, this is the first cytogenetic analysis of chagasic megaesophagus to show that aneuploidies of chromosomes 7, 11, and 17, and TP53 gene deletion might be related to increased risk for malignancy. (C) 2004 Elsevier B.V. All rights reserved.

Human herpesvirus type 6 and type 1 infection increases susceptibility to nonmelanoma skin tumors

In order to investigate herpesvirus (HHV) role in the susceptibility to skin cancer, we compared HHV6 and HHV1 incidence in DNA samples extracted from 120 lesions and 41 normal skin tissues. HHV6 (31.7%) and HHV1 (23.8%) were detected more frequently in skin cancer than in control individuals (14.6 and 5%, respectively) (P=0.0391 and P=0.00094, respectively). The risk of presenting basal cell carcinomas (BCC) was more than 3 times higher for HHV-6 infected patients (OR=3.182; 95% CI: 1.125-8.997). The risk for HHV-1 infected individuals of presenting BCC and squamous cell carcinomas was increased 8 and 6 times, respectively (OR=8.125; 95% CI: 1.735-38.043 and OR=6.290; 95% CI: 1.283-30.856, respectively). (c) 2004 Elsevier B.V.. All rights reserved.

Carcinoma basaloide - Escamoseo de cebeça: relato de 4 casos

Basaloid squamous carcinoma is an aggressive subtype of squamous carcinoma of superior aerodigestive tract. This tumor has been recently described and it seems to have higher incidence in tongue, hypopharynx and supraglottis. It has more agressive biological behavior than pure type of squamous cell carcinoma. We report 4 cases of this tumor and we present a review of the literature.

Papilomavírus humano (HPV) em lesões benignas e malignas de mucosa oral pelos métodos de imuno-histoquímica e hibridização in situ

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Medium-term tongue carcinogenesis assays: A comparative study between 4-nitroquinoline 1-oxide (4NQO)-induced rat and dimethylbenzanthracene (DMBA)-induced hamster carcinogenesis

The most used animal models in oral cancer research are the hamster treated by dimethylbenzanthracene (DMBA), and the rat treated by 4-nitroquinoline 1-oxide (4NQO). The purpose of this study was to compare the DMBA-induced hamster tongue carcinogenesis and 4NQO-induced rat tongue carcinogenesis by means of morphological analysis. Male Wistar rats were distributed into three groups of ten animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. A total of 18 Syrian golden hamsters were submitted to 0.5% DMBA (dissolved in acetone) topical application three times/week for 4, 12 and 20 weeks. The primary histopathological change i.e., hyperplasia and hyperkeratosis, was evidenced after 4 weeks treatment with DMBA. Regarding 12 weeks treatment, 4NQO and DMBA were able to induce morphological changes as depicted by hyperplasia and dysplasia. At 20 weeks, squamous cell carcinoma was found in the majority of animals for both carcinogens used. Taken together, our results suggest that the hamster experimental model disclosed aspects related with tongue carcinogenesis in lesser time than rats. Probably, such discrepancies depend strongly on route of administration and the susceptibility with respect to animal species. © 2006 Elsevier GmbH. All rights reserved.