scholarly journals Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas

2018 ◽  
Vol 18 (4) ◽  
pp. 313-319
Author(s):  
Hale Demir ◽  
Ozgecan Dulgar ◽  
Bugra Taygun Gulle ◽  
Hande Turna ◽  
Sennur Ilvan

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival. There was a significant association between ALDH1 expression and tumor grade (p < 0.001), i.e., the expression of ALDH1 was higher in high-grade tumors. ALDH1 expression was significantly associated with estrogen and progesterone receptor (ER and PR) negativity (p < 0.001) and HER2 positivity (p = 0.001). ALDH1 expression ratios were higher in HER2 type and TNBC. There was a statistically significant correlation between ALDH1 negativity and luminal A subtype (p < 0.001). The overall and disease free survival were shorter in ALDH1+ tumors, although without statistical significance. We confirm that ALDH1 is a potentially important, poor prognostic factor in BC, associated with high histological grade, ER/PR negativity and HER2 positivity. For more accurate results, ALDH1 expression should be evaluated in larger case series including various types/subtypes of BC.

2013 ◽  
Vol 289 (3) ◽  
pp. 1303-1312 ◽  
Author(s):  
Qinglin Li ◽  
Gabriel Eades ◽  
Yuan Yao ◽  
Yongshu Zhang ◽  
Qun Zhou

Previously, we found that basal-like ductal carcinoma in situ (DCIS) contains cancer stem-like cells. Here, we characterize stem-like subpopulations in a model of basal-like DCIS and identify subpopulations of CD49f+/CD24− stem-like cells that possess aldehyde dehydrogenase 1 activity. We found that these cells show enhanced migration potential compared with non-stem DCIS cells. We also found that the chemopreventive agent sulforaphane can target these DCIS stem-like cells, reduce aldehyde dehydrogenase 1 (ALDH1) expression, and decrease mammosphere and progenitor colony formation. Furthermore, we characterized exosomal trafficking of microRNAs in DCIS and found that several microRNAs (miRs) including miR-140, miR-29a, and miR-21 are differentially expressed in exosomes from DCIS stem-like cells. We found that SFN treatment could reprogram DCIS stem-like cells as evidenced by significant changes in exosomal secretion more closely resembling that of non-stem cancer cells. Finally, we demonstrated that exosomal secretion of miR-140 might impact signaling in nearby breast cancer cells.


2015 ◽  
Vol 39 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Ning Xu ◽  
Ming-Ming Shao ◽  
Hai-Tao Zhang ◽  
Mei-Shan Jin ◽  
Yi Dong ◽  
...  

2016 ◽  
Vol 70 (7) ◽  
pp. 625-630 ◽  
Author(s):  
Si-Hyong Jang ◽  
Hyun Deuk Cho ◽  
Ji-Hye Lee ◽  
Hyun Ju Lee ◽  
Soon Auck Hong ◽  
...  

AimsLung cancer is the leading cause of cancer-related deaths worldwide, and it still results in a poor prognosis despite research and development of a treatment modality. Angiomotin (AMOT) was first described as a protein involved in angiogenesis, and although the oncogenic and tumour-suppressive roles of AMOT were recently reported, the biological function of AMOT has not yet been clarified. The aim of this study was thus to evaluate the relationship between reduced AMOT p130 expression and clinicopathological parameters, including patients' survival.MethodsWe enrolled 67 patients with lung adenocarcinoma in this study and measured the immunoreactivity of AMOT p130 in a tissue microarray. The data were analysed using a χ2 test, Cox regression hazards model and log-rank test with Kaplan–Meier curves.ResultsReduced AMOT p130 expression is related to lung adenocarcinoma developed at a young age with statistical significance, but there is no statistical significance for the other clinicopathological parameters. Kaplan–Meier curves with log-rank test showed that reduced AMOT p130 expression had significantly better survival rate compared with the retained group (p=0.002). Univariable and multivariable analyses of the disease free survival revealed that the decreased AMOT expression was an independent prognostic factor (p=0.004, p=0.008, respectively).ConclusionsDecreased AMOT p130 could be an independent indicator of poor survival in patients with lung adenocarcinoma.


2018 ◽  
Vol 91 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Piyabi Sarkar ◽  
Keya Basu ◽  
Pubali Sarkar ◽  
Uttara Chatterjee ◽  
Madhumita Mukhopadhyay ◽  
...  

Background and aim. Breast cancer, a heterogeneous disease, is the most common cause of cancer-related death in women worldwide. Despite considerable developments in treatment modalities, a subset of patients with advanced-stage breast carcinoma display poor prognosis. Breast cancer heterogeneity and risk of recurrence could be explained with the help of cancer stem cell hypothesis. Stem cells have the capacity to self-renew and differentiate into multiple cell types. Aldehyde dehydrogenase-1 (ALDH1), an enzyme responsible for the oxidation of intracellular aldehydes, contributes to normal and tumor stem cell differentiation. Invasion and metastasis in breast cancer are found to be mediated by a subpopulation of tumor cells which exhibit stem cell-like features and express ALDH1. The aim was to document ALDH1 expression in breast carcinoma and find its association with other clinico-pathologic prognostic parameters.Study design. This was a cross-sectional observational study.Methods. A total of 62 patients with breast carcinoma undergoing mastectomy were included in this study. The tumors were classified into molecular subtypes by assessing immunohistochemical (IHC) expression of ER, PgR, HER2 and Ki-67 according to St. Gallen Consensus Conference 2013. ALDH1 expression was studied by IHC and correlated with clinicoathological parameters.Statistical analysis. Statistical analysis was done using Graph Pad software (Prism 5 version) for Windows 7. A p-value <0.05 was considered statistically significant.Results and analysis. Out of 62 tumors, 35 tumors (56.4%) showed ALDH1 positivity. ALDH1 expression was significantly associated with larger size, lymph node involvement, higher grade, higher stage and HER2+ or triple negative tumors.Conclusion. This study suggests that ALDH1 expression is associated with poor prognostic parameters and aggressive tumor behavior. Larger population-based prospective trials on Indian patients are required to validate these results.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1683-1683
Author(s):  
Yanming Zhang ◽  
Wu Depei ◽  
Aining Sun ◽  
Huiying Qiu ◽  
Guangsheng He ◽  
...  

Abstract Abstract 1683 Biphenotypic acute leukemia (BAL) is a very rare type of acute leukemia, which presents a high heterogeneity and poor prognosis. We identified 51 cases (3.0%) BAL from 1693 newly diagnosed acute leukemia patients according to the EGIL scoring system between January 2003 and July 2009. The biological features, treatment and outcome of 39 evaluable BAL patients were analyzed retrospectively. There were 23 (59.0%) cases of myeloid and B-lymphoid (M/B) phenotype, 14 (35.9%) cases of myeloid and T-lymphoid (M/T) phenotype, one case (2.6%) of trilineage phenotype or B-lymphoid and T-lymphoid phenotype respectively. The high expressions of CD34 (84.6%) and HLA-DR (54.5%) on the blast cells of BAL support the notion that BAL probably arises from hemopoietic stem/progenitor cells. It seemed that CD7-positive patients had poorer median survivals comparing with those CD7-negative patients, however, there was no statistical difference (P=0.076). Abnormal karyotypes were detected in 75.7% of 37 BAL patients with valid analysis and displayed a high heterogeneity, which were associated with structural rearrangement and numerical abnormalities including t(8;21) (16.2%), t(9;22) (13.5%), structural rearrangement of 11 chromosome (16.2%), 11q23 (5.4%), complex karyotype (21.6%) and other abnormal karyotypes (10.8%). Combined regimens for both AML and ALL, ALL-type regimens appeared a better complete remission (CR) rate than AML-type regimens (71.4% vs. 63.6% vs. 33.3%). The median survival for overall survival (OS) and disease-free survival (DFS) in our series was 14 and 12 months, the probability of OS and DFS at 2 years was 26.0% and 18.5%, respectively. No statistical differences were observed in CR rate, OS and DFS between M/B and M/T cases. It showed that BAL patients with complex karyotype or rearrangement of 11 chromosome had a significantly worse survival in contrast to normal karyotype, t(8;21) and t(9;22) group (P=0.001). Although BAL with t(8;21) seemed to be appeared a better survival than normal karyotype and t(9;22) group, there were no statistical significance (P=0.436). Our data indicate that combined-type regimens or ALL-based protocols are more effective and complex karyotype, rearrangement of 11 chromosome have the unfavorable prognosis for BAL. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 41 (6) ◽  
pp. 436-441 ◽  
Author(s):  
Daniel A. Rosloff ◽  
Kunal Patel ◽  
Paul J. Feustel ◽  
Jocelyn Celestin

Background: Undifferentiated somatoform (US) idiopathic anaphylaxis (IA) is considered a psychogenic disorder characterized by a lack of observable physical findings and poor response to treatment. Although failure to diagnose true anaphylaxis can have disastrous consequences, identification of US-IA is crucial to limit unnecessary expenses and use of health care resources. Objective: To better define the presentation and understand the potential relationship between US-IA and underlying psychiatric comorbidities. Methods: We retrospectively reviewed 110 visits by 107 patients to our institution for evaluation and management of anaphylaxis over a 1-year period. The patients were classified as having either criteria positive (CP) or criteria negative (CN) anaphylaxis based on whether they met Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium criteria for the clinical diagnosis of anaphylaxis. Patient characteristics, including objective and subjective signs and symptoms, and the presence of psychiatric diagnoses were collected and analyzed. Statistical significance was assessed by using the Fisher exact test. A literature review of US-IA and other psychogenic forms of anaphylaxis was performed. Results: Patients with CP anaphylaxis were more likely to present with hypotension, wheezing, urticaria, and vomiting than were patients with CN anaphylaxis. The patients with CN anaphylaxis were more likely to present with subjective symptoms of sensory throat tightness or swelling compared with patients with CP anaphylaxis. No significant difference was detected in the prevalence of psychiatric conditions between the two groups. Conclusion: Patients who met previously established diagnostic criteria for anaphylaxis were more likely to present with objective physical findings than those who did not meet criteria for true anaphylaxis. CN patients who presented for treatment of anaphylaxis were more likely to present with subjective symptoms. Formal diagnostic criteria should be used by clinicians when evaluating patients with suspected anaphylaxis.


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


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