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Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Endo Y, Hosoda M, Doihara H, Miyoshi S, Yamashita H, Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Socie - Breast Cancer Res. (2016)

Bottom Line: We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups.Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence.Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama-city, Okayama, 700-8558, Japan.

ABSTRACT

Background: The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown.

Methods: In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group.

Results: The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059).

Conclusions: Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of aldehyde dehydrogenase 1 (ALDH1) in breast tumor cells. a Essentially all of the tumor cells are positive for ALDH1. b No ALDH1-positive cells are present
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Fig1: Immunohistochemical staining of aldehyde dehydrogenase 1 (ALDH1) in breast tumor cells. a Essentially all of the tumor cells are positive for ALDH1. b No ALDH1-positive cells are present

Mentions: The majority of specimens contained no ALDH1-positive cells, though some showed a patchy epithelial pattern and identifiable hot spots. ALDH1 expression in all or most of the cells in a hot spot was rare. We evaluated the proportion of ALDH1-positive cells in one hot spot, since cancer stem cells represent only a small fraction of the cell population in a tumor. A representative staining pattern in a breast cancer specimen is shown in Fig. 1. The proportions of ALDH1-positive cells were 0–1 % in 560 cases (early recurrence 81.5 % [150 of 184], late recurrence 86.6 % [116 of 134], no recurrence 91.6 % [294 of 321]), 1–5 % in 47 cases (early recurrence 11.4 % [21 of 184], late recurrence 10.4 % [14 of 134], no recurrence 3.7 % [12 of 321]), and 5–100 % in 32 cases (early recurrence 7.0 % [13 of 184], late recurrence 2.9 % [4 of 134], no recurrence 4.6 % [15 of 321]). Only 11 cases showed more than 20 % of tumor cells to be ALDH1-positive (early recurrence 0.6 % [4 of 184], late recurrence 0.3 % [2 of 134], no recurrence 0.7 % [5 of 321]). In many previous studies, 5 % cutoff points were adopted, but there were few ALDH1-positive cases among those with ER-positive/HER2-negative breast cancer. In the present study, cases with ALDH1-positive rates exceeding 5 % were also very few. We regarded positive cases as those in which more than 1 % of cells were ALDH1-positive, because even a small fraction of cancer stem cells might be an important factor. On the basis of our chi-square test employing the 1 % cutoff value, differences among the three groups were statistically significant (p = 0.004).Fig. 1


Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Endo Y, Hosoda M, Doihara H, Miyoshi S, Yamashita H, Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Socie - Breast Cancer Res. (2016)

Immunohistochemical staining of aldehyde dehydrogenase 1 (ALDH1) in breast tumor cells. a Essentially all of the tumor cells are positive for ALDH1. b No ALDH1-positive cells are present
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930566&req=5

Fig1: Immunohistochemical staining of aldehyde dehydrogenase 1 (ALDH1) in breast tumor cells. a Essentially all of the tumor cells are positive for ALDH1. b No ALDH1-positive cells are present
Mentions: The majority of specimens contained no ALDH1-positive cells, though some showed a patchy epithelial pattern and identifiable hot spots. ALDH1 expression in all or most of the cells in a hot spot was rare. We evaluated the proportion of ALDH1-positive cells in one hot spot, since cancer stem cells represent only a small fraction of the cell population in a tumor. A representative staining pattern in a breast cancer specimen is shown in Fig. 1. The proportions of ALDH1-positive cells were 0–1 % in 560 cases (early recurrence 81.5 % [150 of 184], late recurrence 86.6 % [116 of 134], no recurrence 91.6 % [294 of 321]), 1–5 % in 47 cases (early recurrence 11.4 % [21 of 184], late recurrence 10.4 % [14 of 134], no recurrence 3.7 % [12 of 321]), and 5–100 % in 32 cases (early recurrence 7.0 % [13 of 184], late recurrence 2.9 % [4 of 134], no recurrence 4.6 % [15 of 321]). Only 11 cases showed more than 20 % of tumor cells to be ALDH1-positive (early recurrence 0.6 % [4 of 184], late recurrence 0.3 % [2 of 134], no recurrence 0.7 % [5 of 321]). In many previous studies, 5 % cutoff points were adopted, but there were few ALDH1-positive cases among those with ER-positive/HER2-negative breast cancer. In the present study, cases with ALDH1-positive rates exceeding 5 % were also very few. We regarded positive cases as those in which more than 1 % of cells were ALDH1-positive, because even a small fraction of cancer stem cells might be an important factor. On the basis of our chi-square test employing the 1 % cutoff value, differences among the three groups were statistically significant (p = 0.004).Fig. 1

Bottom Line: We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups.Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence.Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama-city, Okayama, 700-8558, Japan.

ABSTRACT

Background: The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown.

Methods: In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group.

Results: The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059).

Conclusions: Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

No MeSH data available.


Related in: MedlinePlus