Studies on Expression of Aldehyde Dehydrogenase in Normal and Cancerous Tissues of Thyroids

Abstract

Recently published articles have reported the controversial data regarding expression of aldehyde dehydrogenase isozyme 1A1 (ALDH1A1), a potential candidate marker for normal and cancer stem cells (CSCs), in thyroid tissues. These data prompted us to re-evaluate expression of ALDH1A1 in normal and cancerous thyroid tissues by 2 different means. The first method was immunohistochemistry with 2 different anti-ALDH1A1 antibodies from distinct companies. Following validating the integrity of these 2 antibodies by Western blotting with ALDH-expressing and nonexpressing cancer cell lines and immunohistochemistry with breast and colon tissues, we report here significant and comparable expression of ALDH1A1 in both normal and cancerous thyroid tissues with both antibodies. Next, relative expression levels of ALDH isozymes were evaluated by reverse transcription-polymerase chain reaction (RT-PCR), revealing that ALDH1A1 was the most highly expressed isozyme followed by ALDH9A1 and relative expression patterns of isozymes were very similar in normal and cancerous tissues. All these data demonstrate that thyroid cells of normal and cancer origins do express ALDH1A1 and to a lesser extent 9A1. Further study will be necessary to study functional significance of ALDH1A1 in the function and behaviors of thyroid normal and cancer stem cells.

Cancer Stem Cells in the Thyroid

“…In the study by Todaro et al, ALDH1A1 was expressed in a small number of thyroid cancer cells, and the percentages of ALDHA1 expressing cells (3% in FTC, 7% in PTC, and 16% in ATC) were positively correlated with aggressiveness ( 6 ). However, other studies, including ours ( 32 , 33 ), reported much higher positivity rates for ALDH1A1 expression in normal and PTC tissues by immunohistochemistry using the same antibody. Although the reason(s) for these differences is/are at present unclear, and the latter data do not immediately dismiss the significance of ALDH as a CSC marker, Deng et al concluded that “…ALDH should not be used as a CSC marker in tissue types that normally express a high level of ALDH1” ( 29 , 33 ).…”

“…It should be noted here that of the 19 ALDH isozymes, ALDHA1 is the most predominantly expressed in both normal and cancerous thyroid tissues ( 32 ). However, ALDH1A3 is the most highly expressed isozyme in the K1 thyroid cancer cell line mentioned above ( 30 ).…”

Upregulation of stem cell markers ALDH1A1 and OCT4 as potential biomarkers for the early detection of cervical carcinoma

“…In addition, ALDH1A1 may contribute to the majority of ALDH activity in CSCs ( 37 ). The predominant expression of ALDH1A1 has been associated with ALDH activity in prostate and thyroid cancer ( 38 , 39 ). In the case of 6 ALDH1 isoenzymes, ALDH1A1 may be a major contributor of ALDH1 activity and a biomarker for predicting the poor survival of patients with breast cancer ( 40 ).…”

Immunohistochemical expression of ALHD1A1 in thyroid goiter and normal peritumor tissue around papillary thyroid carcinoma in a sample of Iraq patients

“…However, one study revealed that PTC cells showed ALDH1 more than ATC and benign thyroid disorder (29). Nevertheless, other studies have described higher rates for ALDH1A1 expression positivity in normal thyroid tissue as well as PTC (30)(31)(32) (33). Although the possible explanation for these discrepancies is not well established yet (14), besides, the current evidence is strong enough to support the clinical significance of ALDH as biomarker for CSC in thyroid cancer, one study suggested that ALDH should not be utilized as a marker for CSC in tissues that show high ALDH expression under normal conditions (34) (31).…”