Lesões do trato gastrointestinal na síndrome da imunodeficiência adquirida: estudo de 45 necrópsias consecutivas.

This study was designed to evaluate retrospectively the frequency and etiology of the gastrointestinal (GI) lesions in 45 consecutive necropsies of adult patients with Acquired Immunodeficiency Syndrome (AIDS). Gross descriptions and histological sections of the GI tract, from mouth to anus, were reviewed. The slides were H&E stained, and when necessary special stains and immunohistochemical methods were also employed. There were lesions in GI tract in 37 (82.3%) patients; the mouth was the segment most frequently involved (73.3% of the cases), followed by the colon (55.5%). Multiple lesions occurred in 17 (37.7%) cases. Cytomegalovirus caused colonic lesions in 35.7% of the cases. Candidiasis was observed in 26.6% mainly in the mouth and herpes simplex (8.8%) was the important agent of esophageal lesions. Oral hairy leukoplasia associated with HPV was found in 16 (35.5%) cases. Neoplasia was diagnosed in 7 (15.5%) cases: four Kaposi's sarcoma, two anal intramucosal carcinomas and one gastric lymphoma. Our data confirm the high frequency and variety of GI tract alterations in AIDS.

Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma

MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may develop from oral leukoplakia, clinical and histological assessments have limited prognostic value in predicting which leukoplakic lesions will progress. Our aim was to quantify miR expression changes in leukoplakia and same-site OSCC and to identify an miR signature associated with progression. We examined miR expression changes in 43 sequential progressive samples from 12 patients and four non-progressive leukoplakias from four different patients, using TaqMan Low Density Arrays. The findings were validated using quantitative RT-PCR in an independent cohort of 52 progressive dysplasias and OSCCs, and five non-progressive dysplasias. Global miR expression profiles distinguished progressive leukoplakia/OSCC from non-progressive leukoplakias/normal tissues. One hundred and nine miRs were highly expressed exclusively in progressive leukoplakia and invasive OSCC. miR-21, miR-181b and miR-345 expressions were consistently increased and associated with increases in lesion severity during progression. Over-expression of miR-21, miR-181b and miR-345 may play an important role in malignant transformation. Our study provides the first evidence of an miR signature potentially useful for identifying leukoplakias at risk of malignant transformation.

Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?

A significant proportion (up to 62) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68), 9q34.13 (64), 21q22.3 (60), 6p21 and 6q25 (56) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48). DNA losses were observed in 20 of samples and mainly detected on 5q31.2 (35), 16p13.2 (30), 9q33.1 and 9q33.29 (25) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70 of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Proteinprotein interaction networks were created to identify possible pathways associated with OSCC progression.

Oral leukoplakia manifests differently in smokers and non-smokers

Oral leukoplakias (OL) are potentially malignant lesions that are typically white in color. Smoking is considered a risk factor for developing OL, and dysplastic lesions are more prone to malignant transformation. The aim of this study was to describe the clinical features observed in dysplastic and non-dysplastic OL in both smokers and nonsmokers. A total of 315 cases of OL were retrieved and separated into either dysplastic or non-dysplastic lesions, and these cases were further categorized as originating in either smokers or non-smokers. Frequencies of the type of OL lesion, with respect to whether the patients smoked, were established. The results demonstrated that 131 cases of OL were dysplastic (74 smokers and 57 non-smokers), and 184 were non-dysplastic (96 smokers and 88 non-smokers). For OL cases in smokers for which information about alcohol consumption was also available (84 cases), the results revealed no significant difference in the amount of dysplastic and non-dysplastic lesions. Dysplastic lesions were more frequent in male smokers and in non-smoking females. The median age of smokers with cases of OL was significantly lower than in non-smokers; the lowest median ages were observed for female smokers with dysplastic OL. The most frequent anatomical sites of dysplastic lesions were the floor of the mouth in smokers and the tongue in non-smokers. Dysplastic lesions in smokers were significantly smaller than non-dysplastic lesions in non-smokers. Being a male smoker, being female, being younger, and having smaller lesions were associated with dysplastic features in OL. These clinical data may be important for predicting OL malignant transformation.

Oral leukoplakia in China: a review

BACKGROUND: Most prevalence studies on oral leukoplakia (OL) in China have been published in the Chinese language. The present review on the literature in Chinese aimed at making the data available to colleagues who are not familiar with the Chinese language. METHODS: The overall rate and 95% confidence interval of OL were calculated using Excel 2003. RESULTS: Overall prevalence of OL was 9.18% (95%CI = 9.06-9.30%). Gender ratio of prevalence was 8.03:1 (males/females). Prevalence was high in age groups over 40 years with the highest in the group aged 60-69 years (21.04%, 95%CI = 19.95-22.13%). The buccal mucosa was most commonly affected (47.08%, 95%CI = 46.52-47.64%), followed by lip (39.09%), palate (9.85%), gingiva (1.80%), and tongue (1.46%). The prevalence in smokers was 23.43% and in non-smokers 1.93%. Among three variants of smoking, the traditional Hanyan pipe smoking carried the highest risk for the development of OL followed by cigarette and Shuiyan water pipe smoking. The rate of alcohol drinkers with OL was 54.50% and 22.21% in individuals without OL. No case of oral cancer was found in six surveys. CONCLUSIONS: The present data on the prevalence of OL in China are comparable to those in other parts of the world. Some traditional smoking habits, however, are particular to certain regions of China.

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16INK4a in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16INK4a expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16INK4a expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16INK4a and hTERT.

The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.

Correlation between c-Jun and human papillomavirus in oral premalignant and malignant lesions

c-Jun, one of the components of the transcription factor activating protein-1 (AP-1), is suggested as a factor in malignant progression of oral lesions. c-Jun and other AP-1 components relationships with human papillomavirus (HPV) infection have been investigated, but not yet focusing on oral carcinogenesis. The aim of this study was to verify whether c-Jun immunohistochemical expression is related to HPV DNA detection in oral premalignant and malignant lesions. Fifty cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas (OSCC) were submitted to immunohistochemistry to detect c-Jun and to in situ hybridization with signal amplification to assess HPV DNA. It was verified that c-Jun nuclear expression increased according to the degree of dysplasia within the lesion, with the greatest expression in OSCC. The same did not happen concerning HPV infection - a discrete proportional relation was observed in indexes found in leukoplakia with no dysplasia, leukoplakia with dysplasia and OSCC, but statistically insignificant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. Nevertheless, the overall prevalence of HPV infection was 24% and the high-risk HPV types were the most frequently identified, which does not allow excluding HPV as a risk factor in oral carcinogenesis. When relating c-Jun expression and HPV infection, no statistically significant relationship is observed. Results suggest then that malignant progression mediated by c-Jun is independent of the presence of HPV in oral carcinogenesis. (C) 2007 Elsevier Ltd. All rights reserved.

Oral verrucous lesions – a search for PVL

Proliferatiivinen verrukoottinen leukoplakia (PVL) esiintyy yhtenä laajana tai useampana verrukoottisena, valkoisena muutoksena suun limakalvoilla. PVL on aggressiivinen limakalvomuutos, joka ei usein vastaa hoitoihin, uusii herkästi ja sillä on muita leukoplakioita suurempi pahanlaatuistumistaipumus. Tutkimuksen tarkoitus on lisätä tietoa PVL:sta ja sen ilmentymisestä ja kehittymisestä sekä arvioida kriittisesti PVL:n diagnostiikkaa. Systemaattinen kirjallisuuskatsaus suoritettiin etsimällä Pubmed-tietokannan kirjallisuushaulla kaikki englannin kielellä raportoidut ja vertaisarvioidut PVL- potilastapaukset 2000 – 2013. PVL voi histologisesti esiintyä myös verrukoottisena hyperplasiana (VH), joten myös nämä tapaukset sisällytettiin aineistoon. Kaikkiaan 54 artikkelia täytti sisäänottokriteerit. Näissä oli yhteensä 388 PVL- ja 848 VH-tapausta. Lisäksi kerättiin kaikki Turun yliopiston hammaslääketieteen laitoksen suupatologian osastolla histologisesti diagnosoidut vastaavat suun VH-muutokset 2000 – 2013. Kirjallisuudesta havaittiin, että PVL esiintyi useammin naisilla (2,2 : 1), kun taas VH esiintyi useammin miehillä (1 : 3,8). Tupakointi ei näyttänyt liittyvän PVL:aan (30 %), kun taas VH:aan se näytti selkeämmin liittyvän (83 %). PVL:n yleisin sijainti oli ikenellä (59 %) ja suurin osa VH-muutoksista esiintyi posken limakalvolla (51 %). PVL-potilaista 47 %:lla ja VH-potilaista 5 %:lla todettiin seurannassa pahanlaatuinen kasvain. Turun yliopiston suupatologian osastolla diagnosoituja VH-tapauksia oli 13 vuoden aikana 29. Naisten osuus sairastuneista oli suurempi kuin miesten (1,4 : 1). Muutokset esiintyivät yleisimmin kielen limakalvolla (48 %) ja poskessa (34 %). Yhdessä tapauksessa kehittyi pahanlaatuinen kasvain (3 %). Tutkimuksessa todettiin, että PVL- ja VH-muutokset poikkeavat toisistaan sukupuolijakauman, tupakoinnin ja pahanlaatuistumisen osalta. Ongelmana katsauksessa olivat tietojen puutteellisuus ja raportoinnin heterogeenisyys kirjallisuudessa. PVL- ja VH-tutkimuksessa tulisikin panostaa yhteneviin diagnostisiin kriteereihin, jotta materiaalit olisivat vertailukelpoisia. Potilaan kannalta PVL:n ja VH:n varhainen diagnosointi ja huolellinen seuranta ovat olennaisen tärkeitä asioita.

Expression of nonclassical molecule human leukocyte antigen-G in oral lesions

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Increased plasma and salivary cortisol levels in patients with oral cancer and their association with clinical stage

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

Computer-assisted analysis of cell proliferation markers in oral lesions

Abnormalities in any component of the cell cycle regulatory machine may result in oral. cancer, and markers of cell proliferation have been used to determine the prognosis of tumor progression. The aim of this study was to determine whether silver-stained nucleolar organizer region (AgNOR) and Ki-67 measurements could improve the assessment of growth rates in oral lesions. Eighty-three oral biopsies were studied, 20 of which were classified as fibrous inflammatory hyperplasia (FIH), 40 as leukoplakia (LKP) and 23 as oral. squamous cell carcinoma (OSCC). Within the LKP group, 22 out of 29 biopsies were diagnosed as non-dysplastic leukoplakia (LK) and 18 as dysplastic teukoptakia (DLK), presenting discrete, moderate and severe dysplasia. Ki-67 immunotabeting of the lesions increased steadily in the following order: FIH, DLK, LK and OSCC, indicating that Ki-67 is a good marker for predicting the protiferative fraction among benign, premalignant and malignant oral lesions. The median values of AgNOR parameters indicate that the morphometric index gives better results regarding the proliferative rate than the numerical one. A series of linear regressions between AgNOR parameters and Ki-67 showed positive associations. We conclude that a combination of Ki-67 and morphometric AgNOR analyses could be used as an aid in the determination of the protiferative status of oral epithelial. cells in oral cancer. (C) 2007 Elsevier GmbH. All rights reserved.

Potentially malignant epithelial oral lesions: Discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL). PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis. RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%. CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesions. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.

Transformación de leucoplasia verrugosa proliferativa en carcinoma oral: diez años de seguimiento

The authors present a case of proliferative verrucous leukoplakia (PVL) in a 78-year-old man. It was initially presented as leukoplakia on the tongue but a microscopic investigation in 1991 revealed it to be a mild epithelial dysplasia. After 5 years of follow-up, the lesion presented changes in size and location, and a recidivant behavior. In 1996, a red granular and indurated area that appeared on the tongue was found to be a microinvasive squamous cell carcinoma when microscopically investigated. After a review of the clinicopathologic behavior of this entity, the authors concluded that it was a typical PVL, whose diagnosis is difficult and retrospective, as indicated by others. The authors emphasize the importance of periodic detailed clinical and histological examination of this type of lesions in order to detect early signs of malignancy.

Quantitative cell-cycle protein expression in oral cancer assessed by computer-assisted system

The knowledge of cell-cycle control has shown that the capacity of malignant growth is acquired by the stepwise accumulation of defects in specific genes regulating cell growth. Histologic diagnosis might be improved by a quantitative evaluation of more specific diagnosis biomarkers, which could help to precisely identify pre-malignant and malignant oral lesions. The aim of the present study is to evaluate whether computer-based quantitative assessment of p53, PCNA and Ki-67 immunohistochemical expression, could be used clinically to foresee the risk of oral malignant transformation. This retrospective study was carried out in ninety-five oral biopsies, 27 were classified as fibrous inflammatory hyperplasia, 40 as leukoplakia and 28 as oral squamous cell carcinoma. Sixteen out of the 40 leukoplakia were diagnosed as non-dysplastic leukoplakia, the other 24 being dysplastic leukoplakia, of which 50.0% were classified as moderate to severe dysplasia. Comparison of the four groups of oral tissues showed significant rises in p53 and Ki-67 positivity index, which increased steadily in the order benign, pre-malignant, and malignant. In contrast, it was not possible to relate higher PCNA levels with pre-malignant and malignant oral lesions. We therefore conclude that PCNA immunohistochemistry expression is probably an inappropriate marker to identify oral carcinogenesis, whereas joint quantitative evaluation of p53 and Ki-67, appears to be useful as a tumor marker, providing a pre-diagnostic estimate of the potential for cell-cycle deregulation of the oral proliferate status.