Increased salivary aldehyde dehydrogenase 1 in non-reticular oral lichen planus.

BACKGROUND:: Oral lichen planus is a potentially malignant disorder. One of the malignant transformation markers is cancer stem cells. One of the proposed marker for the detection of cancer stem cells's in head and neck cancer is aldehyde dehydrogenase. Recently it is shown that aldehyde dehydrogenase 1 expression in tissue samples is associated with oral lichen planus malignant transformation. OBJECTIVE:: This study evaluates salivary aldehyde dehydrogenase 1 in oral lichen planus. METHOD:: Thirty patients and 30 age and sex-matched healthy volunteers were recruited. Oral lichen planus was diagnosed based on the modified World Health Organization criteria. Subjects in the case group were divided into reticular and non-reticular forms. Unstimulated salivary samples were collected at 10-12 AM. Saliva concentrations of aldehyde dehydrogenase 1 were measured by ELISA. RESULTS:: The differences between aldehyde dehydrogenase levels in the oral lichen planus group compared with the control group were not significant but aldehyde dehydrogenase in non-reticular oral lichen planus was significantly higher than that of the reticular form. LIMITATIONS OF THE STUDY:: This is a cross-sectional study, thus longitudinal studies in oral lichen planus may present similar or different results. CONCLUSIONS:: The mechanism of malignant transformation in oral lichen planus is not defined. Previous analyses revealed that the aldehyde dehydrogenase 1 expression is significantly correlated with increased risk of transformation. This finding is consistent with our results because in the erosive and ulcerative forms of oral lichen planus, which have an increased risk of transformation, salivary aldehyde dehydrogenase 1 was overexpressed. A higher salivary aldehyde dehydrogenase level in non-reticular oral lichen planus can be a defensive mechanism against higher oxidative stress in these groups. Aldehyde dehydrogenase may be one of the malignant transformation markers in oral lichen planus. Further studies are needed for introducing aldehyde dehydrogenase as a prognostic indicator in certain lesions.

Increased salivary aldehyde dehydrogenase 1 in non-reticular oral lichen planus

Abstract: Background: Oral lichen planus is a potentially malignant disorder. One of the malignant transformation markers is cancer stem cells. One of the proposed marker for the detection of cancer stem cells's in head and neck cancer is aldehyde dehydrogenase. Recently it is shown that aldehyde dehydrogenase 1 expression in tissue samples is associated with oral lichen planus malignant transformation. Objective: This study evaluates salivary aldehyde dehydrogenase 1 in oral lichen planus. Method: Thirty patients and 30 age and sex-matched healthy volunteers were recruited. Oral lichen planus was diagnosed based on the modified World Health Organization criteria. Subjects in the case group were divided into reticular and non-reticular forms. Unstimulated salivary samples were collected at 10-12 AM. Saliva concentrations of aldehyde dehydrogenase 1 were measured by ELISA. Results: The differences between aldehyde dehydrogenase levels in the oral lichen planus group compared with the control group were not significant but aldehyde dehydrogenase in non-reticular oral lichen planus was significantly higher than that of the reticular form. Limitations of the study: This is a cross-sectional study, thus longitudinal studies in oral lichen planus may present similar or different results. Conclusions: The mechanism of malignant transformation in oral lichen planus is not defined. Previous analyses revealed that the aldehyde dehydrogenase 1 expression is significantly correlated with increased risk of transformation. This finding is consistent with our results because in the erosive and ulcerative forms of oral lichen planus, which have an increased risk of transformation, salivary aldehyde dehydrogenase 1 was overexpressed. A higher salivary aldehyde dehydrogenase level in non-reticular oral lichen planus can be a defensive mechanism against higher oxidative stress in these groups. Aldehyde dehydrogenase may be one of the malignant transformation markers in oral lichen planus. Further studies are needed for introducing aldehyde dehydrogenase as a prognostic indicator in certain lesions.

Lymphocyte-predominant triple-negative breast carcinomas in premenopausal patients: Lower expression of basal immunohistochemical markers.

OBJECTIVES: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic. MATERIALS AND METHODS: We reviewed all the original histological sections to assess pathological features, and to select a representative area for tissue microarrays and immunohistochemical study. Estrogen and progesterone receptors, HER2 and Ki-67 were evaluated in whole histological sections. The following markers were analyzed in tissue microarrays sections: androgen receptor, cytokeratin 5/6, cytokeratin 14, epidermal growth factor receptor (EGFR), vimentin, p16, claudin-3, -4, and -7, p63, and aldehyde dehydrogenase isoform 1 (ALDH1). Lymphocyte-predominant breast cancer (LPBC) was defined by the presence of more than 50% of lymphocytes in the intratumoral stroma. RESULTS: Twenty-six (22.4%) patients present tumors classified as LPBC and 90 (77.6%) as non-LPBC. The two groups were similar regarding age of patients, tumor grade and Ki-67 positive cells. LPBC cases presented lower frequency of expression of the basal cytokeratins, EGFR, and basal-like immunoprofile. There was a trend to higher expression of ALDH1 by stromal intratumoral cells. The expression of all other markers were similar in the two groups. CONCLUSIONS: Lymphocyte-predominant TNBC in premenopausal patients are mostly of non-basal phenotype.

ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma / Immunoexpressão de ALDH1 e CD44 como indicador de prognóstico de invasão e metástase em carcinoma epidermoide de boca

Oral squamous cell carcinoma (OSCC) is one of the most common cancer in the head and neck and results in high morbidity and mortality annually, being the worst prognosis related to the presence of metastasis in cervical lymph nodes. Metastasis has been associated with a subpopulation of tumor cells, called cancer stem cells (CSCs), which consists of a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to other ordinary tumor cells from the tumor bulk. The aim of present study was to evaluate the immunoexpression of the CSC markers ALDH1 and CD44 in primary sites of OSCC and corresponding metastatic lymph nodes, by means of immunohistochemistry. The immunolabeling was further correlated with clinicopathological data. Archived Formalin-fixed, Paraffin-embedded tumor tissue specimens (n=50) and corresponding metastatic lymph nodes (n=25) were obtained from 50 patients with OSCC after surgical treatment. CD44 and ALDH1 immunostaining were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic cervical lymph nodes as a whole. The percentage of ALDH1 and CD44 positive tumor cells as well as immunostaining intensity was graded and a combined score, ranging from 0 to 9 (ALDH1) or 0 to 12 (CD44), was obtained by multiplying both parameters. Next, combined scores were dichotomized into a final score classified as low (ALDH1≤ 2; CD44≤ 4) or high (ALDH1> 2; CD44> 4) immunoexpression. ALDH1 and CD44 immunoexpression was detected in both primary and metastatic tumor sites, although with different immunolabeling pattern. ALDH1-positive tumor cells consisted of scattered patches and no immunoexpression was observed within keratin pearls. Conversely, CD44 immunopositivity was more homogeneous and widely distributed, with higher labeling in peripheral areas of the tumor islands within the tumor invasion front. Although not statistically significant, the means of ALDH1high (p= 0.0985) and CD44high (p= 0.1632; Mann- Whitney post-test) immunoexpression were higher in metastatic lymph nodes compared to primary tumors. ALDH1high was positively associated (p= 0.0184) with perivascular invasion, while CD44high was positively associated (p= 0.0186; Fisher's Exact Test) with metastasis (N+). Five-year survival rates tended to be lower in patients with ALDH1high immunoexpression compared to ALDH1low, although with no statistical significance (p= 0.1303). In summary, the present study revealed that CD44 is highly labeled in tumor cell from metastatic sites, being associated with lymph node metastasis, while ALDH1 high immunostaining was associated with perivascular invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with OSCC invasion and metastasis.(AU)

O carcinoma epidermóide de boca (CEB) é uma das neoplasias mais comuns da região de cabeça e pescoço e resulta em alta morbidade e mortalidade anualmente, estando o pior prognóstico relacionado à presença de metástase em linfonodos cervicais. O processo de metástase tem sido associado a uma subpopulação de células tumorais, chamadas células-tronco de câncer (CSC, do inglês Cancer stem cells), que consistem em uma pequena população de células com propriedades de células-tronco, incluindo maior taxa de migração e potencial metastático em comparação com outras células tumorais. O objetivo do presente estudo foi avaliar os marcadores candidatos de CSCs ALDH1 e CD44 em tumores primários de CEB e metástases linfonodais correspondentes, por meio de imuno-histoquímica. A imunomarcação foi posteriormente correlacionada com dados clínico-patológicos. Foram obtidas amostras de tecido tumoral parafinado fixado em formalina (n = 50) e os linfonodos metastáticos correspondentes (n = 25) de 50 pacientes com CEB submetidos somente ao tratamento cirúrgico. Os marcadores CD44 e ALDH1 foram analisados de forma semi-quantitativa de acordo com a proporção e intensidade de células positivas no fronte de invasão e em linfonodos cervicais metastáticos como um todo. A porcentagem de células tumorais ALDH1 e CD44 positivas, bem como a intensidade da imunomarcação, foi classificada em um escore combinado obtido pela multiplicação de ambos os parâmetros, variando de 0 a 9 (ALDH1) ou 0 a 12 (CD44). Em seguida, as pontuações combinadas foram dicotomizadas em um escore final classificado como baixo (do inglês low) (ALDH1 ≤ 2; CD44 ≤ 4) ou alto (do inglês high) (ALDH1> 2; CD44> 4). A imunoexpressão de ALDH1 e CD44 foi detectada tanto em tumores primários quanto em linfonodos cervicais metastáticos, embora com padrão diferente de imunomarcação. Células tumorais ALDH1-positivas foram identificadas como focais e dispersas ao longo do fronte de invasão, sem imunomarcação nas pérolas córneas. Em contraste, a imunopositividade para CD44 foi mais homogênea e amplamente distribuída, com maior imunomarcação em áreas periféricas das ilhotas tumorais presentes no fronte de invasão. Embora não estatisticamente significativa, as médias da imunoexpressão ALDH1high (p = 0.0985) e CD44high (p = 0.1632, pós-teste de Mann-Whitney) foram maiores em linfonodos metastáticos em comparação com tumores primários. ALDH1high foi positivamente associado com invasão perivascular (p = 0.0184), enquanto CD44high foi com metástase (N+) (p = 0.0186; teste exato de Fisher). As taxas de sobrevida global em 5 anos tenderam a ser mais baixas em pacientes com imunoexpressão elevada de ALDH1 em comparação com ALDH1low, embora sem significância estatística (p = 0.1303). Em resumo, o presente estudo revelou que a elevada imunomarcação de CD44 está significativamente associada com metástases linfonodais, enquanto que a elevada imunomarcação de ALDH1 está associada com invasão perivascular. Em conjunto, sugerimos que a imunoexpressão de CD44 e ALDH1 esteja relacionada com o fenótipo de células tronco de câncer que tem capacidade de invasão e metástase em CEB.(AU)

Aldehyde dehydrogenase isoform 1 (ALDH1) expression as a predictor of radiosensitivity in laryngeal cancer.

BACKGROUND: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. METHODS: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. RESULTS: ALDH1 expression was detected in 17.5 % (10/57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1-. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 + group versus 48.9 % for ALDH1- patients (p = 0.034). CONCLUSION: The patients in this study with ALDH1 + tumours had better outcomes than their counterparts with ALDH1- tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed.

Liver cancer stem cells are selectively enriched by low-dose cisplatin

Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs). Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT) assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1) and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

Liver cancer stem cells are selectively enriched by low-dose cisplatin.

Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs). Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 µg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT) assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1) and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 µg/mL cisplatin, whereas 5 µg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas.

BACKGROUND: CD44 and aldehyde dehydrogenase 1 (ALDH1) are considered putative markers of highly tumorigenic cells (i.e., cancer stem-like cells) in head and neck squamous cell carcinomas. This small subset of cells is believed to be the primary responsible for tumor initiation and progression. The objectives of this study were (i) to evaluate the patterns of CD44 and ALDH1 expression in the tumor center and in the invasive front, as well as in adjacent non-tumor epithelium, and (ii) to correlate these findings with clinical parameters. MATERIALS AND METHODS: The sample comprised 44 patients with primary head and neck squamous cell carcinomas. Hematoxylin and eosin (HE) staining was used for histopathological tumor grading and for morphological analysis of adjacent non-tumor epithelium. Semiquantitative analysis was performed in histological sections immunostained for CD44 and ALDH1. RESULTS: ALDH1 immunostaining in the invasive front showed positive association with tumor size, regional metastasis, tumor histopathological grading, and disease progression. Moreover, expression of this marker in both tumor invasive front and adjacent non-tumor epithelium was related with more aggressive tumors. CD44 immunostaining was heterogeneous in all areas evaluated and did not show association with clinical data. CONCLUSION: Collectively, these data suggest that ALDH1 immunostaining in the invasive front and in adjacent non-tumor epithelium may help identify tumors with a more aggressive behavior, potentially contributing to improving treatment customization and the monitoring of patients with head and neck cancer.