Herramientas invasivas y no invasivas para el diagnóstico de cáncer oral: revisión de la literatura / Invasive and non-invasive tools for the diagnosis of oral cancer: review of the literature

El cáncer oral es una neoplasia frecuente a nivel mundial; su diagnóstico se realiza de forma tardía por lo menos en un 50-60 por ciento de los casos, lo que empeora el pronóstico de los pacientes, ya que a mayor estadio, mayor es la tasa de mortalidad. Por lo tanto, es fundamental contar con herramientas que permitan realizar un diagnóstico temprano y tratamiento oportuno, sobre todo cuando existen lesiones premalignas clínicamente identificables. En el presente estudio se revisan las herramientas invasivas y no invasivas (modernas y antiguas) que han demostrado utilidad para el diagnóstico de cáncer oral; se basan tanto en técnicas ampliamente disponibles en la práctica clínica como en otras aún no disponibles, pero que podrían implementarse con una apropiada coordinación entre el profesional dedicado a la clínica y los investigadores.

Oral cancer is a neoplasm that is frequent on a worldwide level andis diagnosed late in at least 50-60% of the cases. Its late detection worsens the prognosis of patients because it is associated with a greater mortality. Therefore, it is essential to have tools that allow a timely diagnosis when premalignant lesions present and when there are noclinically identifi able premalignant lesions. In the present study, wereview the invasive and non-invasive tools (modern and old) that haveproven useful for the diagnosis of oral cancer; they are based bothon techniques widely available in clinical practice and on techniques not yet available, but that could be implemented with appropriate coordination between the clinic professional and the researchers.

Inmunoexpresión de E-cadherina y vimentina en mucosa oral normal, displasia epitelial oral y carcinoma oral de células escamosas / Immunoexpression of E-cadherin and vimentin in normal oral mucosa, oral epithelial displasia and oral squamous cell carcinoma

El objetivo fue evaluar la inmunoexpresión de E-cadherina y Vimentina en mucosa oral normal (MON), displasia epitelial oral (DEO) y carcinoma oral de células escamosas (COCE). Se realizó un estudio descriptivo de una serie de casos analizandolos mediante técnica de inmunohistoquímica contra E-cadherina y Vimentina 16 muestras de MON, 16 de DEO y 19 de COCE. La inmunotinción fue evaluada cualitativamente considerando extensión e intensidad para E-cadherina e intensidad para Vimentina. El análisis de la extensión e intensidad de la inmunotinción de E-cadherina y Vimentina según diagnóstico reveló una asociación estadísticamente significativa (p<0,001). Siendo la expresión de E-cadherina más alta en MON, seguido por DEO y más baja en COCE, inversamente a lo que se observó con Vimentina. El presente estudio reveló la subregulación del marcador molecular E-cadherina junto con la expresión aberrante por parte de células epiteliales del marcador mesenquimal Vimentina en muestras de MON, DEO y COCE.

The aim was to evaluate the expression of E-cadherin and Vimentin in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC), in comparison with normal oral mucosa (NOM) in a descriptive case study using immunohistochemistry. A total of fifty-one (N=51) histological samples were included; as follows: n = 16 (NOM), n = 16 (OED) and n = 19 (OSCC). All samples were analyzed using immunohistochemistry against the expression of E-cadherin and Vimentin. Immunostaining was qualitatively evaluated by extent and intensity of its expression for E-cadherin and intensity for Vimentin. Extension and intensity analysis of E-cadherin and Vimentin immunostaining according to group revealed a statistically significant association (r<0.001). E-cadherin expression was found to be highest in NOM followed by OED and lowest in OSCC, inverse to what was observed with Vimentin. The present study revealed the down regulation of the molecular marker E-cadherin, suggestive of reduction in dysplastic cells on comparison to NOM cells, and aberrant expression of the mesenchymal marker Vimentin by epithelial cells in samples of NOM, OED and OSCC; questioning their value as a prognostic marker.

Immunoexpression of cell proliferation markers in oral squamous cell carcinoma / Inmunoexpresiones de marcadores de proliferación celular en carcinoma de células escamosas orales

This study aimed to assess the immunoexpression of cell proliferation markers (Ki-67 and Mcm-2) in oral tongue cancer, correlating it with patients' age and prognostic indicators. Sample was composed of 22 cases under 40 years and 22 over 50 years of age. Clinical staging and histological grade of malignancy were obtained. Cell proliferation was evaluated through labeling indices. Statistical analysis was performed (p<0.05 for statistical significance). Most young patients were stages III/IV (n=13/65 %) and most older patients were stages I/II (n=11/61.1 %) (p>0.05). Mean Ki-67-LI in young and older patients was 42.4 % and 44.15 %, respectively (p>0.05). Mean Mcm-2-LI was higher in older (63.6 %) than in young patients (55.75 %) (p<0.05). We found that young patients presented more aggressive lesions in comparison to older patients, however Mcm-2 expression was significantly higher in older than in young patients. SCC of tongue can be more aggressive in young patients, and this may not be related to cell proliferation. Our findings for Mcm-2 LI and Ki-67 LI suggests that Mcm-2 could be a more sensitive marker for cell proliferation.

Este estudio tuvo como objetivo evaluar la inmunoexpresión de marcadores de proliferación celular (Ki-67 y Mcm-2) en el cáncer de lengua oral, correlacionándolo con la edad de los pacientes y los indicadores pronósticos. La muestra estuvo compuesta por 22 personas menores de 40 años y 22 personas mayores de 50 años. Se identificaron los estadios clínicos y el grado histológico de malignidad. La proliferación celular se evaluó mediante índices de marcado. Se realizó análisis estadístico (p <0,05 para significación estadística). La mayoría de los pacientes jóvenes eran estadios III / IV (n = 13/65 %) y la mayoría de los pacientes mayores eran estadios I / II (n = 11 / 61,1 %) (p> 0,05). La media de Ki-67-LI en pacientes jóvenes y mayores fue 42,4% y 44,15%, respectivamente (p> 0,05). La media de Mcm-2-LI fue mayor en pacientes mayores (63,6 %) que en pacientes jóvenes (55,75 %) (p <0,05). Se encontró que los pacientes jóvenes presentaron lesiones más agresivas en comparación con los pacientes mayores, sin embargo la expresión de Mcm-2 fue significativamente mayor en pacientes mayores que en pacientes jóvenes. SCC de la lengua puede ser más agresivo en pacientes jóvenes, y esto no puede estar relacionado con la proliferación celular. Nuestros hallazgos para Mcm-2 LI y Ki-67 LI sugieren que Mcm-2 podría ser un marcador más sensible para la proliferación celular.

Analysis of serum and salivary immunoglobulin M in patients with orofacial epithelial cancers.

Context: The physiological changes in the humoral immune system of patients with orofacial epithelial cancers (OECs) are considered key factors in the pathogenesis, prognosis, and management of these individuals. Aim: This study assessed the serum and salivary immunoglobulin M (IgM) levels in patients with OECs. Settings and Designs: This is a cross-sectional study of the serum and salivary IgM profile among patients with OEC and healthy controls. Materials and Methods: There were 78 subjects comprising 30 patients with untreated OEC, 18 patients with OEC receiving treatment and 30 healthy, age and gender matched individuals. The serum and salivary samples from the participants were analyzed for IgM using the enzyme linked immunosorbent assay technique. Results: The mean value of serum IgM in OEC patients receiving treatment was significantly lower compared to untreated OEC patients and healthy controls (P = 0.01). However, the mean serum IgM among untreated OEC patients was not significantly different compared with healthy controls. In contrast, the salivary IgM level did not show any significant difference among the three groups (P = 0.06). Furthermore, there was no correlation between the serum and salivary levels of IgM among the subjects. Conclusion: The findings from this study suggest that serum IgM levels in OEC patients receiving treatment might be good biomarker while salivary IgM may not be reliable as a marker in these individuals.

Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth

The aim of this study was to evaluate the immunoexpression of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth and to correlate the results with demographic, survival, clinical (TNM staging) and histopathological variables (tumor grade, perineural invasion, embolization and bone invasion). Data from medical records and diagnoses of 41 patients were reviewed. Histological sections were subjected to immunostaining using primary antibodies for human MMP-2, MMP-9 and CD31 and streptavidin-biotin-immunoperoxidase system. Histomorphometric analyses quantified positivity for MMPs (20 fields per slide, 100 points grade, ×200) and for CD31 (microvessels <50 µm in the area of the highest vascularization, 5 fields per slide, 100 points grade, ×400). Statistical design was composed by non-parametric Mann-Whitney U test (investigating the association between numerical variables and immunostainings), chi-square frequency test (in contingency tables), Fisher's exact test (when at least one expected frequency was less than 5 in 2×2 tables), Kaplan-Meier method (estimated probabilities of overall survival) and Iogrank test (comparison of survival curves), all with a significance level of 5%. There was a statistically significant correlation between immunostaining for MMP-2 and lymph node metastasis. Factors associated negatively with survival were N stage, histopathological grade, perineural invasion and immunostaining for MMP-9. There was no significant association between immunoexpression of CD31 and the other variables. The intensity of immunostaining for MMP-2 can be indicative of metastasis in lymph nodes and for MMP-9 of a lower probability of survival.

O objetivo deste estudo foi avaliar a imunoexpressão de MMP-2, MMP-9 e CD31/densidade microvascular em carcinomas espinocelulares de soalho bucal e correlacionar os resultados com variáveis demográficas, de sobrevida, clínicas (estadiamento TNM) e histopatológicas (grau de diferenciação tumoral, invasão perineural, embolização e invasão óssea). Dados de prontuários e de diagnósticos de 41 pacientes foram revisados. Cortes histológicos foram submetidos à imunomarcação usando anticorpos primários para MMP-2, MMP-9 e CD31 humanos e sistema streptoavidina-biotina-imunoperoxidase. Análise histomorfométrica quantificou a positividade para MMPs (20 campos, grade de 100 pontos por lâmina, ×200) e para CD31 (microvasos <50 µm na área de maior vascularização, 5 campos, grade de 100 pontos por lâmina, ×400). O planejamento estatístico foi composto pelo teste não paramétrico U de Mann-Whitney (verificação da associação entre variáveis numéricas e imunomarcações), teste de frequências do qui-quadrado (em tabelas de contingência), teste exato de Fisher (quando pelo menos uma frequência esperada foi menor do que 5 em tabelas 2×2), método de Kaplan-Meier (estimativa de probabilidades de sobrevida global) e teste de Iogrank (comparação das curvas de sobrevida), todos com nível de significância de 5%. Houve correlação estatisticamente significante entre imunomarcação para MMP-2 e metástase em linfonodo. Os fatores relacionados negativamente com a sobrevida foram estadiamento N, gradação histopatológica, invasão perineural e imunomarcação de MMP-9. Não houve associação significativa entre imunoexpressão de CD31 e as demais variáveis. A intensidade de imunomarcação para MMP-2 pode ser indicativa de metástase em linfonodo e para MMP-9 de uma menor probabilidade de sobrevida.

Immunomorphological assessment of regional lymph nodes for predicting metastases in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma is the most common neoplasm and comprises of approximately 80% of the cancers occurring in the oral cavity. The role of the host response to this neoplasm has been recognized, and for many years the regional lymph node in tumor-bearing hosts has been considered as an anatomic barrier to the systematic dissemination of tumor cells. Morphological evaluation of the regional nodes has aided in understanding the immune response. Aim: The current study was carried out to observe the morphological changes occurring in the regional lymph nodes and to evaluate whether these features could be helpful in assessing the immunological status of the patient, and thereby, the prognosis of the patient. Materials and Methods: The study was based on lymph nodes from 63 patients with oral squamous cell carcinoma, who underwent radical neck dissection or modified neck dissection. In the lymph node, four morphological patterns were observed that included lymphocyte predominance, germinal center predominance, mixed pattern (sinus Histiocytosis), and an unstimulated pattern. The cases were then divided into four groups according to the predominant immunoreactivity pattern based on the World Health Organization (WHO) standardized system for reporting human lymph node morphology. Results: Revealed that risk of metastases to cervical lymph nodes in patients with lymphocyte predominance was less (28.6%) when compared to the high risk of metastases with germinal center predominance (68%), and these results were statistically significant (P < 0.05). Patients with a mixed pattern showed less risk of metastases (45.4%), while those with an unstimulated pattern had increased risk of metastases (66.6%), but the results were not statistically significant. It was also found that in the positive nodes, germinal center hyperplasia (50.2%) was the predominant pattern. Conclusion: The present study revealed that patients with lymphocyte predominance had less risk of metastases and patients with germinal center predominance had a high risk of metastases to the lymph node.

Densidade de mastócitos e microdensidade vascular em displasias epiteliais e carcinomas orais / MVD and mast cell density in vascular epithelial dysplasia and oral carcinomas

Os tumores malignos orais representam 5% de todos os cânceres humanos e o carcinoma escamocelular oral (CECO) corresponde a 90% destes casos. Sabe-se que as pessoas acometidas por displasia epitelial oral (DEO) apresentam um maior risco de desenvolver CECO. A angiogênese está associada à iniciação e progressão neoplásica, sendo o início da neovascularização em DEOs um pré-requisito para a formação do tumor. Na angiogênese, destacam-se os mastócitos, responsáveis por estimular e manter a formação da rede vascular em determinadas doenças, inclusive displasias e neoplasias. Estas células liberam fatores que estimulam a angiogênese, como o VEGF. Assim, este estudo se propôs a avaliar o papel dos mastócitos na angiogênese de DEO e CECO, considerando parâmetros clínicos e morfológicos, comparando-os entre si. Metodologia: Quatorze DEOs e 56 CECOs, dispostos em lâminas convencionais e de tissue microarray (TMA), respectivamente, provenientes do Hospital AC Camargo, foram imunomarcardas para os anticorpos anti-CD34, anti-VEGF-A e anti-Mast cell tryptase, os três primeiros através do sistema EnVision Advance™ (Dako Corporation, Carpinteria, USA) e o último através do sistema Histofine (Nichirei Biosciences Inc., Tokyo, Japan). A microdensidade vascular (MDV - vasos/mm2) foi estabelecida através da determinação do número de vasos marcados para CD34 em cinco áreas de hot spot; a expressão de VEGF-A foi determinada pelo escore imuno-histoquímico (EI) estabelecido por Sinicrope et al. (1995); finalmente, a densidade da mastócitos (DM – células/ mm2) foi determinada através do número de células contadas em cinco áreas de hot spot. Resultados/Conclusões: A DM não apresentou relação com parâmetros clínicos e morfológicos em DEOs e CECOs, não existindo diferença na atividade exercida por Ms granulados e degranulados (p=0,18 e p= 0,1439, respectivamente; Teste de Mann-Whitney). A DM foi significativamente maior entre os casos de DEO quando comparadas aos carcinomas (p=0,01; Teste de Mann-Whitney), o que parece envolver a ação das células neoplásicas infiltrantes na regulação negativa do número de Ms nestes tumores. A MDV, nos casos de DEO e CECOs, não esteve associada aos parâmetros clínicos e morfológicos das mesmas, possivelmente sugerindo que a densidade de vasos não contribui de maneira independente para a progressão e comportamento biológico destas lesões. Os casos de DEO apresentaram MDV significativamente maior em relação aos CECOs (p= 0,0003, Teste de Mann-Whitney), sugerindo-se como possível causa uma subanálise dos vasos nas lâminas de TMA. A expressão de VEGF, no epitélio e lâmina própria, não esteve relacionada aos parâmetros clínicos e histológicos em DEOs e CECOs, tampouco à progressão de DEO para CECO, uma vez que os maiores EI foram encontrados em CECO bem diferenciado, seguido de DEO moderada, CECO moderadamente diferenciado e DEO discreta. A DM (granulados e degranulados) não estava correlacionada à MDV, o que provavelmente aponta para a atuação destas células, de maneira mais expressiva, em outros cânceres. Também não existiu correlação significante entre a DM, granulado e degranulado, e expressão de VEGF nestas duas lesões, o que provavelmente demonstra que não há participação expressiva dos Ms na produção desta citocina. Por fim, existiu associação entre a expressão de VEGF por células tumorais e MDV (r= 0,39, p= 0,0299, Teste de Spearman), o que parece demonstrar uma maior propensão das células tumorais infiltrantes para exercerem atividade sobre o desenvolvimento da MDV em CECOs...

Immunohistochemical staining of Langerhans cells in HPV-positive and HPV-negative cases of oral squamous cells carcinoma

The Human Papillomavirus (HPV) has been strongly implicated in development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved in such mechanism of defense Langerhans cells (LC) stand out, which are responsible for processing and presenting antigens. OBJECTIVES: The purposes of this study were to investigate the presence of HPV DNA and to evaluate the immunohistochemical reactivity for Langerhans cells between HPV-positive and HPV-negative OSCC. Twenty-seven cases of OSSC were evaluated. MATERIAL AND METHODS: DNA was extracted from paraffin-embedded tissue samples and amplified by Polymerase Chain Reaction (PCR) for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the Streptavidin-biotin technique. RESULTS: From the 27 cases, 9 (33.3 percent) were HPV-positive and 18 (66.0 percent) HPV-negative. HPV 18 was the most prevalent viral type (100 percent cases) and infection with HPV-16 (co-infection) was detected in only 1 case. In the OSCC specimens examined, immunoreactivity to S-100 antibody was detected in all cases, with a mean number of 49.48±30.89 Langerhans cells positive for immunostaining. The mean number of immunostained Langerhans cells was smaller in the HPV-positive cases (38 cells/case) than in the HPV-negative cases (42.5 cells/case), but this difference was not significant (p=0.38). CONCLUSIONS: The low frequency of detection of HPV DNA in OSCC indicates a possible participation of the virus in the development and progression of only a subgroup of these tumors. There was no association between the immunohistochemical labeling for Langerhans cells (S-100+) and HPV infection of in OSSC. These findings suggest that the presence of HPV in such OSCC cases could not alter the immunological system, particularly the Langerhans cells.

Rol de las características clínicas e histológicas como factores pronósticos para la sobrevida en pacientes con carcinoma de células escamosas de la cavidad oral / Oral squamous cell carcinoma: restrospective analysis of 36 cases

Background: Survival of patients with oral squamous cell carcinoma is low and depends mostly on TNM staging of the tumor. Aim: To perform a retrospective analysis of a series of patients with oral squamous cell carcinoma. Material and Methods: Retrospective review of patients with the diagnosis, seen between 1995 and 2006 in a regional hospital. Host inflammatory response and pattern of tumor invasion were assessed using the staging proposed by Bryne et al. Results: The medical records of 36 patients aged 39 to 89 years, were reviewed. During the study period, 15 patients died. Better survival was associated to a low pattern of tumor invasion and a high inflammatory response and the topographic location of the tumor. Conclusions: Inflammatory response, tumor invasion and location are associated with survival in oral squamous cell carcinoma.

Introducción: El carcinoma de células escamosas de la cavidad oral (CCECO) es una patología cuyo comportamiento es producto de interrelaciones con el huésped, esto es, por el patrón de invasión (PI) histopatológica y la respuesta inflamatoria (RI). El objetivo de este estudio es analizar las características clínicas e histopatológicas como factores pronóstico, en términos de supervivencia (SV) en pacientes con CCECO. Material y Método: Serie de casos. Se incluyeron pacientes diagnosticados en el Hospital Regional de Talca y Hospital Base de Curicó entre los años 1995 y 2006. Se revisaron las fichas clínicas y biopsias de 36 pacientes con CCECO. Se determinó el Frente Invasivo Tumoral (FIT), evaluándose los parámetros propuestos por el sistema de graduación de Bryne (PI y RI) y factores de importancia clínica como localización topográfica de la lesión, edad y género, relacionándolos con SV mediante curvas de Kaplan-Meier y Log Rank test. Posteriormente, se aplicó una regresión de Cox para obtener un análisis multivariado y cálculo de RR. Del total de casos del estudio, 15 pacientes fallecieron por CCECO. Resultados: La mayor SV se asoció a un bajo escore de PI y una alta RI respectivamente (RR 1,5). La localización topográfica de la lesión se relacionó significativamente con la SV, no así el grupo de edad. Conclusiones: Nuestros resultados sugieren que la ubicación de la lesión es un factor importante en el pronóstico de la enfermedad y que una respuesta inmune/inflamatoria adecuada, expresada en un bajo escore de RI, mejora el pronóstico de SV en pacientes con CCECO.

Evaluation of circulating immune complexes and serum immunoglobulins in oral cancer patients - A follow up study.

Background: High serum immunoglobulins and circulating immune complexes (IgG, IgM, IgA and CIC) values in patients with cancer have been used as tumor markers. Hence, the aim of the study was to estimate these immunological markers in pre- and post-treatment phases with a follow-up of 3-24 months and to understand the prognostic significance of the same in patients with oral cancer. Materials and Methods: The malignancy group consisted of 56 patients with different stages (AJCC TNM) of oral cancer and 20 healthy control group. Samples were selected at random and subjected for sequential analysis of serum biochemical markers (IgG, IgA, IgM and CIC-circulating immune complexes levels) in the pre- and post-treatment period. Statistical method employed was the paired t test. Results: We observed significant elevated levels of all the immunological markers ( P < 0.01) when compared with the control group. Sequential analysis of these markers revealed significant reduction in immunological markers in stage I and II patients. On the contrary, stage III and IV patients showed remarkably elevated levels of IgA and CIC one year after initial treatment. Conclusions : All these immunological markers are indicative of tumor burden and Serum levels of CIC and IgA might be employed as prognostic indicators in oral cancer.

Modulação da resposta imune em pacientes portadores de queilite actínica e carcinoma espinocelular de boca / Modulation of immune response in patients with actinic cheilitis and oral squamous cell carcinoma

Programmed death-1 (PD-1) é uma proteína de membrana que funciona como um importante regulador negativo da atividade de linfócitos ativa dos, participando, desta forma, do delicado balanço entre ativação e tolerância de células T. Dados recentes têm evidenciado que os mecanismos de tolerância periférica, mediados pela interação PD-1/PD- L1, também impedem uma resposta imune antitumoral eficaz, mesmo em condições nas quais os antígenos tumorais possam ser reconhecidos. Apesar de crescentes evidências demonstrarem o papel da via PD-1 no escape tumoral, pouco se sabe a respeito do seu significado em tumores da cavidade oral. Sabe-se menos ainda sobre a expressão desta molécula em lesões orais pré-neoplásicas. Baseado no exposto, o presente estudo analisou a expressão de PD-1 e seu ligante PD-L1 em lesões de queilite actínica e carcinoma espinocelular de boca através de citometria de fluxo e imunomarcação in situo Os resultados obtidos demonstraram que as células isoladas do sangue periférico e de lesões de queilite actínica e carcinoma espinocelular oral apresentam expressão aumentada de PD-1. A expressão de PD-L1 é mais restrita em queilite actínica, porém é intensa em carcinoma espinocelular oral.

Programmed death-1 (PD-l) is a transmembrane protein that acts as a negative regulator in effector T cells, modulating the delicate balance between effective antimicrobial immune defenses and immune-mediated tissue damage. However, recent evidences suggest that the PD-l: PD-L1 pathway can also block antitumor immune responses even when tumor antigens can be recognized. In spite of growing data indicating the involvement of PD-l in tumor escape, little is known about its role in tumors of oral cavity. In addition, the involvement of PD-l in pre-malignant lesions is an important issue to be clarified. In the present work we investigated the expression of PD-l and PD-L1 in blood and biopsies of patients with actinic cheilitis and oral squamous cell carcinoma by flow cytometry, immunofluorescence and immunohistochemistry. Our data showed that Iymphocytes obtained from peripheral blood and lesion sites exhibited high expression of PD-l in both groups studied Moreover, PD-L1 expression was intense in oral squamous cell carcinoma and moderate in actinic cheilitis.

p53 Immunoexpression in oral squamous cell carcinomas from different anatomical sites: a comparative study

RESUMEN: Las alteraciones de la p53 han sido implicadas en el proceso de carcinogénesis oral. El carcinoma de células escamosas es la malignidad más común de la cavidad oral, siendo la lengua el sitio afectado con mayor frecuencia. El objetivo de este estudio ha sido comparar la inmunoexpresión de la p53 en 43 muestras de carcinoma de células escamosas de la cavidad oral (CCEOs) de 5 sitios anatómicos distintos: lengua, piso bucal, encía/crista alveolar, región retromolar y otras regiones de la cavidad oral. Treinta y tres lesiones (el 76,8%) han mostrado positividad para la p53 (índice promedio del 48,37%). No han sido encontradas diferencias estadísticamente significantes entre la expresión de p53 y los diferentes sitios orales analizados. Similarmente, no han sido encontradas diferencias cuando comparadas las lesiones de lengua con los sitios remanentes. Estos resultados parecen sugerir la no existencia de diferencias entre los sitios anatómicos orales en cuanto a la inmunoexpresión de la p53. Además de eso, otros mecanismos, además de las alteraciones de la p53, en los CCEs de lengua, pueden tener relevancia en la mayor agresividad tumoral encontrada en este sitio anatómico en particular.

Fatores de prognóstico da queilite actínica analisados por imuno-histoquímica e citometria estática: estudo comparativo com leucoplasias associadas a displasias, e carcinomas espinocelulares / Prognostic parameters of actinic cheilitis analysed by immunohistochemical and estatic cytometry: comparative study with leukoplakia combined with dysplasia and squamous cell carcinoma

As lesöes cancerizáveis podem manter-se estáveis, regredir ou sofrer transformaçöes neoplásica. Nos fatores de prognóstico, classicamente estabelecidos, repousam dogmas e elevado grau de subjetividade. Para caracterizar a expressäo imuno-histoquímica de p53, CD31, TGFx e PCNA e avaliar o conteúdo de DNA nuclear pela citometria estática foram selecionados 13 casos de queilite actínicas. Nove casos de hiperplasias, 12 casos de leucoplasias e 13 casos de neoplasias, situados no lábio, foram submetidos aos mesmos exames. Os resultados indicaram as alteraçöes da proteína p53 como as mais significativas nas queilites actínicas. Em lesöes positivas para p53, 50 por cento apresentaram um conteúdo aneuplóide, indicando a precocidade destas alteraçöes e assimilando sua propensäo para malignidade. Nas queilites actínicas, a marcaçäo do TGFx exibiu um padräo intermediário entre lesöes hiperplásicas e neoplásicas. Os índices de proliferaçäo, obtidos pela expressäo de PCNA, foram crescentes a partir das lesöes hiperplásicas até os carcinomas. A densidade vascular, aferida pela contagem de vasos marcados com CD31, apresentou padräo similar. Na análise de citometria de imagem, todas as lesöes hiperplásicas mostraram conteúdo diplóide. As queilites actínicas e leucoplasias, em nove casos, apresentaram histogramas aneuplóides. Os carcinomas exibiram padräo aneuplóide em dez casos. A expressäo dos marcadores p53, CD31, PCNA e TGFx e a mensuraçäo da ploidia, foram caracterizadas em lesöes de queilites actínicas, podendo ser utilizadas como indicadores de prognóstico nas lesöes cancerizáveis

Immunological studies in oral submucous fibrosis.

Oral submucous fibrosis (OSMF) is a high risk precancerous condition. The possible role of immunological factors in the pathogenesis of this condition was evaluated in 113 cases and 25 controls. The male/female ratio was 1.5/1. The mean age of males was significantly lower than that of females. The mean ESR levels were within normal limits, but for a higher than 20 mm fall per hr. in 40% of the cases. The serum IgA, IgG, and IgM levels were elevated significantly as compared to the controls. Circulating auto-antibodies and tissue-deposited antibodies were also found in 33% and 40% of the cases, respectively. From the analysis of the results, it is difficult to ascribe an auto-immune basis for the causation of OSMF. The female bias and elder age group, the factors generally considered in favour of an immune disorder, was not found in our study. However, raised ESR in 40% and serum globulin levels in 47% of the patients, distinctly higher levels of serum immunoglobulins, and positivity for circulating and tissue deposited antibodies in 33% and 34% of the cases respectively, do indicate an immunological basis. Therefore, further studies are required to ascertain the role of cellular immune mechanism and genetic parameters to explain the etiopathogenesis of this complex clinical entity.