ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions

Abstract: Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Expression and clinicopathologic significance of aldehyde dehydrogenase 1 and human epidermal growth factor receptor in gastric adenocarcinoma / 解放军医学杂志

Objective To investigate the expression of aldehyde dehydrogenase 1 (ALDH1) and human epidermal growth factor receptor (HER-2) in human gastric cancer tissues, and analyze its relationship with clinicopathological characteristics. Methods The surgical specimens, gastroscopic biopsy specimens and clinicopathological data of 162 patients with gastric cancer treated in Hengshui People's Hospital Affiliated to Hebei Medical University from July 2015 to March 2018 were selected. The expressions of ALDH1 and HER-2 protein in gastric cancer tissues and paracancerous tissues of 162 patients were detected by immunohistochemistry. The relationship between the results and clinicopathological characteristics were analyzed. Results ALDH1 and HER-2 protein were significantly higher in gastric cancer tissues (48.7%, 34.0%) than those in paracancerous tissues (8.0%, 11.7%, P<0.05). The expression of ALDH1 protein was significantly related to T state, histological differentiation, TNM stage, lymph node metastasis and distant metastasis (P<0.05), but had no relationship with gender, age and tumor location. The expression of HER-2 protein was significantly related to T state, tumor location, histological differentiation, TNM stage and distant metastasis (P<0.05), but had no relationship with gender, age and lymph node metastasis. ALDH1 expression was positively associated with HER-2 (P<0.00). Conclusions ALDH1 and HER-2 are upregulated in gastric cancer. ALDH1 and HER-2 may promote the development of gastric cancer and serve as new therapeutic targets for gastric cancer.

Expression and Clinical Significance of ALDH1 and ABCG2 in Cervical Cancer Cells / 实用妇产科杂志

Objective:To detect the expression of ALDH1 and ABCG2 in the specimens from different levels of cervical lesions.Methods:Use SP immunohistochemistry to detect the expression of ALDH1 and ABCG2 in 76 cases of cervical squamous cancers,52 cases of HSIL,and 37 cases of chronic cervicitis tissues,and analyze the results.Results:①The positive expression rates of ALDH1 and ABCG2 in chronic cervicitis tissues were 5.41％ (2/37) and 8.11％ (3/37),in HSIL tissues were 23.08％ (12/52) and 28.85％ (15/52),and in cervical cancers tissues were 53.95％ (41/76) and 61.84％ (47/76),respectively.The positive expression rates in cervical cancers tissues were significantly higher than in HSIL and Cc hronic cervicitis tissues,(P ＜ 0.05).②The positive expression of ALDH1 in cervical cancer tissues had correlation with tumor grade and lymphnode metastasis (P ＜0.05),while the positive expression of ABCG2 in cervical cancer tissues had correlation with tumor grade,clinical stage and lymph-node metastasis(P ＜0.05).③The expressions of ALDH1 and ARCG2 in cervical cancer were positive relative(r =0.535,P ＜ 0.05).Conclusions:The increased expressions of ALDH1 and ABCG2 in cervical squamous cancer may play a role in the occurrence,development and metastasis of cervical squamous cell carcinoma.ALDH1 and ABCG2 may have synergistic effect in occurrence of cervical cancer.

Expressions and clinical significances of aldehyde dehydrogenase 1 and transforming growth factor-β2 in triple negative breast cancer / 国际肿瘤学杂志

Objective To investigate the expressions and clinical significances of breast cancer stem cell markers such as aldehyde dehydrogenase 1 (ALDH1) and transforming growth factor-β2 (TGF-β2) in patients with triple negative breast cancer.Methods Samples of 60 triple negative breast cancer tissues were investigated for the expressions of ALDH1 and TGF-β2 proteins by immunohistochemical staining.The correlation analysis,disease-free survival analysis and overall survival analysis were performed.Results The positive expressions of ALDH1 protein and TGF-β2 protein in the 60 breast cancer primary lesions were 23 cases (38.33％) and 38 cases (63.33％) respectively.The expression of ALDH1 protein was not correlated with tumor size (x2 =0.307,P =0.580),histological grade (x2 =4.244,P =0.120),clinical stage (x2 =0.982,P =0.612) or lymph node metastasis (x2 =1.111,P =0.292).The expression of TGF-β2 protein was not correlated with histological grade (x2 =4.651,P =0.098),lymph node metastasis (x2 =3.513,P =0.061),clinical stage (x2 =1.310,P =0.519) or tumor size (x2 =0.629,P =0.428).The disease-free survival time [(38.43±3.86) months vs.(53.38 ±2.58) months] and the overall survival time [(42.00±3.11) months vs.(53.84 ± 2.19) months] of ALDH1-positive patients were significantly shorter than those of ALDH1-negative patients,and the differences were statistically significant (x2 =8.490,P =0.004;x2 =11.270,P =0.001).The disease-free survival time [(42.81 ±3.32) months vs.(54.72 ±2.50) months] and the overall survival time [(44.74 ± 2.68) months vs.(57.18 ± 1.55) months] of TGF-β2 positive patients were significantly shorter than those of TGF-β2-negative patients,and the differences were statistically significant (x2 =4.300,P =0.038;x2 =8.900,P =0.003).The expression of ALDH1 protein was positively correlated with the expression of TGF-32 protein (r =0.360,P =0.005).Conclusion The ALDH1 phenotype is an independent predictor of poor prognosis.The activation of TGF-32 signaling pathway may be involved in the regulation of triple-negative breast cancer stem cells.

Influence of stem-like cells on EMT occurrence in mice with triple-negative breast can-cer and on their biological behavior / 中国肿瘤临床

Objective:To discuss the influence of ALDH1+and CD133+phenotypic breast cancer stem-like cells in TA2 triple negative breast cancer on promoting epithelial-mesenchymal transition (EMT) occurrence in TA2 mice with triple-negative breast cancer and on their biological behavior. Methods:Flow cytometry was performed to analyze the markers ALDH1 and CD133 in TA2 mice triple nega-tive breast cancer and breast cancer stem-like cells with ALDH1+, ALDH1?, CD133+, and CD133?phenotypes, which were sorted out. Then, the TA2 mice were inoculated with sorted tumor cells according to cell type. The mice were divided into ALDH1+, ALDH1?, CD133+, and CD133-groups. The tumor-growing conditions were observed. A tumor tissue was sliced for the immunohistochemical testing of ALDH1?, CD133?, and EMT-related Twist1, E-cadherin, and VE-cadherin proteins. The expression difference of breast cancer stem cell surface markers ALDH1 and CD133 in triple-negative breast cancer and EMT-related proteins Twist1, E-cadherin, and VE-cad-herin was analyzed. Results:The expression rates of breast cancer stem cell markers ALDH1 and CD133 in TA2 mice triple negative breast cancer were 31.2%and 6.5%, respectively. The tumor growth ability of TA2 mice from ALDH1+group was obviously stronger than that from ALDH1?group. The CD133+group was evidently stronger than CD133?group. The immunohistochemical results showed that ALDH1, Twist1, and VE-cadherin expression levels in the ALDH1+group were evidently higher than that in the ALDH1?group (all P<0.05). E-cadherin expression decreased (P<0.05). CD133?, Twist1, and VE-cadherin expression levels in CD133+group were higher than that in CD133?group (all P<0.05). Conclusion:In TA2 mice triple negative breast cancer, ALDH1+and CD133+phenotypic breast cancer stem-like cells may influence the expression of EMT-related proteins, and promote the formation of triple-negative breast cancer.

Research advances in biomarkers of the prognosis of breast cancer / 天津医药

Breast cancer has become the most common malignant tumor and the major cause of cancer-related death for women around the world. The number of patients shows an increasing trend recently. Breast cancer is a big threaten to wom?en’s health and quality of life. With the development of molecular biology, molecular biomarkers have been found assiciated with prognosis in patients with breast cancer, which makes it possible to predict cancer patient survival precisely and practi?cally. This review summarized those new developments of biomarkers on the prognosis of breast cancer.

Correlation between expression of ALDH1/ABCG2 and microvessel for-mation in epithelial ovarian cancer / 中国病理生理杂志

AIM:To elucidate the correlation between the expression of aldehyde dehydrogenase 1 (ALDH1)/ATP-binding cassette subfaminly G member 2 ( ABCG2 ) and microvessel density ( MVD ) in epithelial ovarian cancer ( EOC) .METHODS:In 198 specimens of EOC and 60 specimens of ovarian benign epithelial tumor tissues , the protein expression of ALDH1/ABCG2 and CD105 ( microvessel marker ) was detected by immunohistochemical staining .RE-SULTS:The positive rates of ALDH1 and ABCG2 in the EOC were 64.1%and 61.6%, respectively , while the positive rates in benign epithelial tumor tissues were 8.3%and 6.7%, respectively , and there were significant differences between them (P<0.05).In EOC and benign epithelial tumor tissues , the MVD were 22.6 ±9.7 and 5.03 ±3.35, respectively, and the difference was also significant (P<0.05).The expression of ALDH1 and ABCG2 in EOC was significantly related to differentiation, FIGO stage,and abdominal organ and lymph node metastasis (P<0.05).MVD had correlation with dif-ferentiation, FIGO stage, ascite, and abdominal organ and lymph node metastasis (P<0.05).MVD had positive correla-tion with the expression of ALDH1 and ABCG2 (P<0.01).There was also a positive correlation between the expression of ALDH1 and ABCG2 ( P<0.01) .Over-expression of ALDH1/ABCG2 and MVD≥23 were related to the poor prognosis . The survival rates in ALDH1/ABCG2 positive and MVD≥23 groups were significantly lower than those in ALDH 1/ABCG2 negative and MVD<23 groups (P<0.05).The FIGO stage, the expression of ALDH1/ABCG2 and MVD were indepen-dent prognosis factors of EOC ( P<0.05 ) .CONCLUSION: The results suggest that the expression of ALDH 1/ABCG2 and MVD in EOC are related to differentiation , lymph node metastasis , clinical stage and prognosis .Combined detection of these indexes may play an important role in predicting the progression and prognosis of EOC .

Prognostic Impact and Clinicopathological Correlation of CD133 and ALDH1 Expression in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: CD133 and aldehyde dehydrogenase 1 (ALDH1) expression are reliable poor-prognosis markers associated with the presence of adverse biomarkers and subtypes of breast cancer. The aim of our study was to investigate and compare the clinical impact of CD133 and ALDH1 expression in invasive breast cancer. METHODS: A total of 291 consecutive patients with invasive breast cancer who underwent breast cancer operations from 2005 to 2010 at a single institution were included in this retrospective review. CD133 and ALDH1 expression were determined by immunohistochemistry. RESULTS: CD133 and ALDH1 expression were positive in 24.7% and 22.0% of the patients, respectively, and were associated with tumor size, cancer stage, estrogen receptor negativity, nonluminal subtype, triple-negative breast cancer, and recurrence. CD133 expression was significantly associated with lymph node metastasis, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, chemotherapy, and poor disease-free (p=0.002) and overall survival (p=0.014), but ALDH1 expression was not. Cancer stage (p<0.001) was an independent prognostic factor for disease-free survival in multivariate analysis. Cancer stage (p<0.001) and receipt of radiotherapy (p=0.045) were independent prognostic factors for overall survival in multivariate analysis. CONCLUSION: CD133 or the combination of CD133 and ALDH1 expression were more widely associated with the presence of adverse biomarkers and subtypes of breast cancer, compared to ALDH1 expression alone, and these markers may have a potential predictive role and be a helpful tool in the management for patients with invasive breast cancer.

Expression of tumor stem cell marker ALDH1 in invasive bladder cancer tissue and its relationship with clinicopathological parameters and prognosis / 吉林大学学报(医学版)

Objective To study the expression of tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1)in invasive bladder cancer tissue and to clarify its relationship with the biological behavior of bladder cancer. Methods The ALDH1 expression in 109 cases of primary invasive carcinomas specimens (case group)and 20 cases of normal bladder tissue surrounding cancer (control group)was detected by immunohistochemistry. At the same time,the ALDH1 expression in 6 cases of metastatic pelvic lymph node tissue and 20 cases of non-metastatic pelvic lymph node tissue was detected. The relationship between the ALDH1 expression and the chinicopathological charateristics of invasive bladder cancer and its influence in the survival rate and disease-free survival were analyzed. Results The positive rates of ALDH1 expression in bladder cancer tissue and normal bladder tissue were 33.94%(37/109)and 5.00% (1/20),respectively,there was significant different between them (P<0.01);they were 19.05% (8/42)and 43.28% (29/67)in the cases with non muscle invasive and nmuscle invasive bladder cancer, respectively,there was significant difference (P<0.01);they were 13.04% (3/23)and 39.53% (34/86)in the cases of bladder cancer with low grade and high grade,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 12.90% (4/31)in the tissue of bladder cancer with metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 0.00%(0/20)in the metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.01).The overall survival rate in the patients with positive ALDH1 expression was 64.9% while it was 84.7% in negative ones,there was significant difference (P<0.05);the disease-free Survival was 51.4% and 75% in the patients with positive and negative ALDH1 groups,respectively,there was significant difference (P<0.05). Conclusion The high expression of tumor stem cell marker ALDH1 is associated with staging, grading and prognosis of invasive bladder cancer.ALDH1 may play a role in the tumorigenesis,progression and metastasis of bladder cancer.

Research of expression of aldehyde dehydrogenase 1 and breast cancer resistance protein and their correlation in breast cancer / 中国癌症杂志

Background and purpose:Resistance to antitumor agents is a major cause of treatment failure in patients with breast cancer. Research has shown that, tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1) is related with some anticancer drugs (such as cyclophosphamide, cisplatin) resistance, and the content of ALDH1 in tumor cells after treatment is higher than that before treatment. Breast cancer resistance protein (BCRP) is not expressed in normal tissues, but high expressed in breast cancer of after treatment, it may be associated with the mechanism of tumor drug resistance. This study was to investigate the correlation between expression and the relationship between these two kinds of protein ALDH1, BCRP and clinical pathological characteristics. Methods:Immunohistochemistry was performed to detect the expression of ALDH1 and BCRP in breast inifltrating ductal carcinoma tissues, and whether there is a correlation between and explore their relationship with clinical pathological features and their expression. Results:The expression of ALDH1 protein and BCRP protein in breast cancer and paracarcinoma breast tissues has signiifcant difference(χ2=14.685, P=0.000;χ2=12.243, P=0.000).The expression of ALDH1 with patients age, pathologic stage, axillary lymph node metastasis, histological grading, ER, PR, and HER-2 state were not relevant(P>0.05). HER-2, BCRP protein, expression was higher in cancer tissue (χ2=5.289, P=0.021). There were no relevant with the expression of BCRP with patients age, pathologic stage, axillary lymph node metastasis and histological grading, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2) (P>0.05). Conclusion:ALDH1 proteins may be an independent factor compared with occur drug resistant protein, and participate breast cancer drug resistance in the chemotherapy and tumor invasion and metastasis of malignant biological behavior.

Study on aldehyde dehydrogenase-1 tumor cells in invasive micropapillary carcinoma of the breast / 中华内分泌外科杂志

Objective To investigate the expression of tumor stem cell marker aldehyde dehydrogenase -1 (ALDH-1)in primary tumor and lymph node metastases of lymph node-positive invasive micropapillary carcinoma ( IMPC) of breast and its clinical significance .Methods The expression , location and distribution of ALDH-1 were examined by immunohistochemical staining in 103 cases with lymph node metastasis of IMPC and 110 cases with lymph node metastasis of invasive ductal carcinoma not otherwise specified ( IDC-NOS) without preoperative chemotherapy and radiotherapy , and their relationship with clinicopathological characteristics and prognostic sig-nificance was analyzed .Results ( 1 ) The positive expression rate of ALDH-1 was significantly higher in IMPC group of primary tumor and lymph node metastases (37.9% in primary tumor, 39/103 cases;47.6% in lymph node metastases, 49/103 cases)than in IDC-NOS group(21.8% in primary tumor, 24/110 cases; 23.6% in lymph node metastases, 26/110 cases)(P<0.05).(2)Expression of ALDH-1 had a significantly positive corre-lation with tumor size , histological grade , lymph node metastasis , ER-negative status , PR-negative status , and HER2 overexpression in primary tumor and lymph node metastases of IMPC (P<0.05).(3)The disease-free sur-vival of IMPC group patients was significantly shorter than that of IDC-NOS group patients(P=0.003).In IPMC patients with lymphode metastases , the disease-free survival of patients with ALDH-1 positive in primary tumor and lymph node was significantly lower than patients with ALDH-1 negative expression (P<0.05).In multivari-ate analysis, positive expression of ALDH-1 in metastatic lesions was associated with worse prognosis ( P =0.005).Conclusion ALDH-1 can be used as an independent factor for predicting prognosis of patients with lymph node-positive breast IMPC and the existence of stem cells in IMPC tumor cells may represent high IMPC lymphatic invasion , lymph node metastasis and high resistance .

Expression and clinical significance of aldehyde dehydrogenase 1 in nasopharyngeal squamous carcinoma / 肿瘤研究与临床

Objective To investigate the significance of aldehyde dehydrogenase 1 (ALDH1)expression in appraising the prognosis of nasopharyngeal squamous carcinoma (NPC).Methods The expression of ALDH1 protein was detected by immunohistochemistry in human specimens obtained from 120 NPC patients without the history of radiotherapy or chemothetapy.Results A relatively high expression of ALDH1 were observed in 40.0 ％ (48/120) patients of NPC,the expression of ALDH1 in the edge of the cancer nests and stroma,particularly spindle cancer cells were strongly positive.The positive expression of ALDH1 was closely associated with patients' nasopharyngeal tumor size (P =0.011),lymphatic metastasis (P =0.005) and clinic stage (P =0.001),but not associated with their gender and age (both P ＞ 0.05).The Kaplan-Merier and Cox regression analysis indicated that ALDH 1 closely correlated with clinical progrosis of the patients.It showed that ALDH1 was an independent risk factor which may affect the prognosis of NPC patients.Conclusion The expression of ALDH1 protein closely correlate with clinic outcome of NPC,suggesting that ALDH1 is a risk factor for clinic progrosis of NPC patients.

Expression of aldehyde dehydrogenase 1 in human rectal carcinoma tissues and its prognostic significance / 肿瘤

Objective: To investigate the expression of CSC (cancer stem cell) and SC (stem cell) co-expressed marker ALDH1 (aldehyde dehydrogenase 1) in rectal carcinoma tissues and its clinical significance. Methods: The expressions of ALDH1 in rectal carcinoma tissues and the corresponding para-carcinoma tissues from 50 cases of rectal carcinoma were detected by indirect fluorescence antibody staining. The relationship between the expressions of ALDH1 and the clinicopathological features of patients with rectal carcinoma was analyzed. The five-year survival rate was estimated by Kaplan-Meier method. Results: The positive expression rate of ALDH1 in rectal carcinoma tissues was higher than that in the para-carcinoma tissues (P < 0.05). The expression level of ALDH1 was associated with tumor differentiation, Duke's stage, and TNM stage (P < 0.05). The five-year survival rate of patients with positive expression of ALDH1 was lower than that of patients without ALDH1 expression (P < 0.05). Conclusion: The expression of ALDH1 is associated with certain clinicopathological features and the five-year survival rate of patients with rectal cancer. Copyright © 2013 by TUMOR.

Expression of aldehyde dehydrogenase 1 in breast cancer and its clinical significance / 肿瘤

Objective:The purpose of this study is to investigate the expression of tumor stem cell marker aldehyde dehydrogE-nase 1 (ALDH1) in breast cancer and its clinical significance. Methods:The expression of ALDH1 protein was examined by immunohistochemical staining in 92 breast cancer tissues. The correlation analysis and diseasE-free survival analysis of patients was evaluated based on the clinical follow-up data. Results:Expression of ALDH1 protein had a significant correlation with progesterone receptor (PR) and cerb-B2 (P0.05). The 2-year diseasE-free survival rate of AlDH1-positive patients was lower than that of ALDH1-negative patients (P<0.05). ALDH1-positive patients, who received CEF regimen chemotherapy and hormone therapy, had lower 2-year diseasE-free survival rate than that of ALDH1-negative patients (P<0.05). Conclusion:The decreased diseasE-free survival rate of ALDH1-positive patients is related with drug resistance. ALDH1 could be used as an independent factor for predicting the prognosis of breast cancer.