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ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

Bottom Line: We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay.ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

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Correlation between ALDH1 immunoreactivity and patients’ clinical outcome in ovarian serous and clear cell carcinoma.A H-E staining and ALDH1 immunohistochemical staining of primary ovarian serous adenocarcinoma (left) and primary ovarian clear cell adenocarcinoma (right) Upper left panel: H-E staining of ALDH1high specimen. Upper right panel: ALDH1 immunohistochemical staining of ALDH1high specimen. Lower left panel: H-E staining of ALDH1low specimen. Lower right panel: ALDH1 immunohistochemical staining of ALDH1low specimen. Magnification of images: ×400. B Log-rank test for ALDH1high/low groups of ovarian serous adenocarcinoma and clear cell adenocarcinoma patients. Serous adenocarcinoma: 62 cases/clear cell adenocarcinoma: 37 cases. Cases in the ALDH1high group are cases with positive ratio for ALDH1 of over 20% for serous adenocarcinoma cases and 15% for clear cell adenocarcinoma cases. Left: column: progression-free survival (PFS). Right column: overall survival (OS). *P values.
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pone-0065158-g006: Correlation between ALDH1 immunoreactivity and patients’ clinical outcome in ovarian serous and clear cell carcinoma.A H-E staining and ALDH1 immunohistochemical staining of primary ovarian serous adenocarcinoma (left) and primary ovarian clear cell adenocarcinoma (right) Upper left panel: H-E staining of ALDH1high specimen. Upper right panel: ALDH1 immunohistochemical staining of ALDH1high specimen. Lower left panel: H-E staining of ALDH1low specimen. Lower right panel: ALDH1 immunohistochemical staining of ALDH1low specimen. Magnification of images: ×400. B Log-rank test for ALDH1high/low groups of ovarian serous adenocarcinoma and clear cell adenocarcinoma patients. Serous adenocarcinoma: 62 cases/clear cell adenocarcinoma: 37 cases. Cases in the ALDH1high group are cases with positive ratio for ALDH1 of over 20% for serous adenocarcinoma cases and 15% for clear cell adenocarcinoma cases. Left: column: progression-free survival (PFS). Right column: overall survival (OS). *P values.

Mentions: A total of 123 epithelial ovarian cancer tissues were immunohistochemically stained with anti-ALDH1 antibody (Table 3, Figure 6A). The medians of ALDH1-positive rates in serous adenocarcinoma cases and clear cell adenocarcinoma cases were 20% and 15%, respectively. We therefore divided the cases into two groups, ALDH1high group and ALDH1low group, according to the medians. As shown in Table 3, there was no significant correlation of the expression level of ALDH1 with age or with each FIGO clinical stage. High expression level of ALDH1 showed no significant correlation with advanced stages (stage III+IV), T factor or lymph node metastasis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. The log-rank test revealed that higher expression level of ALDH1 is associated with poorer prognosis with a significant difference in OS of patients with serous adenocarcinoma (P = 0.006) and OS of patients with clear cell adenocarcinoma (P = 0.047) than those of lower expression level of ALDH1 (Figure 6B). Higher expression level of ALDH1 showed a tendency for shorter PFS than that of lower expression level of ALDH1, but the differences were not significant (serous adenocarcinoma: P = 0.062; clear cell adenocarcinoma: P = 0.058).


ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

Correlation between ALDH1 immunoreactivity and patients’ clinical outcome in ovarian serous and clear cell carcinoma.A H-E staining and ALDH1 immunohistochemical staining of primary ovarian serous adenocarcinoma (left) and primary ovarian clear cell adenocarcinoma (right) Upper left panel: H-E staining of ALDH1high specimen. Upper right panel: ALDH1 immunohistochemical staining of ALDH1high specimen. Lower left panel: H-E staining of ALDH1low specimen. Lower right panel: ALDH1 immunohistochemical staining of ALDH1low specimen. Magnification of images: ×400. B Log-rank test for ALDH1high/low groups of ovarian serous adenocarcinoma and clear cell adenocarcinoma patients. Serous adenocarcinoma: 62 cases/clear cell adenocarcinoma: 37 cases. Cases in the ALDH1high group are cases with positive ratio for ALDH1 of over 20% for serous adenocarcinoma cases and 15% for clear cell adenocarcinoma cases. Left: column: progression-free survival (PFS). Right column: overall survival (OS). *P values.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3675199&req=5

pone-0065158-g006: Correlation between ALDH1 immunoreactivity and patients’ clinical outcome in ovarian serous and clear cell carcinoma.A H-E staining and ALDH1 immunohistochemical staining of primary ovarian serous adenocarcinoma (left) and primary ovarian clear cell adenocarcinoma (right) Upper left panel: H-E staining of ALDH1high specimen. Upper right panel: ALDH1 immunohistochemical staining of ALDH1high specimen. Lower left panel: H-E staining of ALDH1low specimen. Lower right panel: ALDH1 immunohistochemical staining of ALDH1low specimen. Magnification of images: ×400. B Log-rank test for ALDH1high/low groups of ovarian serous adenocarcinoma and clear cell adenocarcinoma patients. Serous adenocarcinoma: 62 cases/clear cell adenocarcinoma: 37 cases. Cases in the ALDH1high group are cases with positive ratio for ALDH1 of over 20% for serous adenocarcinoma cases and 15% for clear cell adenocarcinoma cases. Left: column: progression-free survival (PFS). Right column: overall survival (OS). *P values.
Mentions: A total of 123 epithelial ovarian cancer tissues were immunohistochemically stained with anti-ALDH1 antibody (Table 3, Figure 6A). The medians of ALDH1-positive rates in serous adenocarcinoma cases and clear cell adenocarcinoma cases were 20% and 15%, respectively. We therefore divided the cases into two groups, ALDH1high group and ALDH1low group, according to the medians. As shown in Table 3, there was no significant correlation of the expression level of ALDH1 with age or with each FIGO clinical stage. High expression level of ALDH1 showed no significant correlation with advanced stages (stage III+IV), T factor or lymph node metastasis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. The log-rank test revealed that higher expression level of ALDH1 is associated with poorer prognosis with a significant difference in OS of patients with serous adenocarcinoma (P = 0.006) and OS of patients with clear cell adenocarcinoma (P = 0.047) than those of lower expression level of ALDH1 (Figure 6B). Higher expression level of ALDH1 showed a tendency for shorter PFS than that of lower expression level of ALDH1, but the differences were not significant (serous adenocarcinoma: P = 0.062; clear cell adenocarcinoma: P = 0.058).

Bottom Line: We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay.ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

Show MeSH
Related in: MedlinePlus