Abstract

Abstract [Introduction and Purpose] Cancer stem cells (CSCs) may have abilities of self-renewal and multi-potent differentiation and be responsible for tumor initiation, progression, metastasis and highly resistant to radiation or chemotherapy. Aldehyde dehydrogenase 1 (ALDH1) enzymes are a family of intracellular enzymes that participate in cellular detoxification, differentiation and drug resistance through the oxidation of cellular aldehydes. The biochemical function of CD133 currently remains unclear, but its expression on the cell surface has been demonstrated to be a specific marker for CSCs in many malignant tumors. ALDH1 and CD133 have been identified as putative CSCs marker in patients with lung adenocarcinoma (ad patients) (Miyata et al, 2015). In this study, we investigated the relationship CSCs markers (ALDH1 and CD133 expression) and various clinical parameters in ad patients. We also showed that the expression of CSCs markers (ALDH1 and CD133 expression) related with prognostic potential in ad patients. [Materials and Methods] We examined 92 of 154 (59.7%) in Japanese ad patients, who underwent surgical resection in Fukuoka-Wajiro Hosp. Those 92 ad sections were performed immunohistochemical (IHC) staining for ALDH1 and CD133 using a standard immunoperoxidase technique. The staining intensity of cytoplasmic staining of ALDH1 was scored as 0, 1, 2, or 3, corresponding to negative, weak, intermediate, or strong immunoreactivity, respectively. Percentage of cells with positive ALDH1 was graded as 0 to 100%. The ALDH1-score was assigned to each case by multiplying the intensity score by the each percentage of cells staining. The ALDH1-score was calculated as follows: H = (% of cells that stained at intensity category 1 × 1) + (% of cells that stained at intensity category 2 × 2) + (% of cells that stained at intensity category 3 × 3). We defined as positive cases when more than 100 of the ALDH1-score were calculated. We also defined as CD133 positive cases when more than 10% of tumor was stained (negative cases; > 10% positivity, positive cases; < 10% positivity). [Results] The mean of the ALDH1-score from 92 cases was 52.1. The ALDH1-score of stage II-IV disease (59.1) seemed to be higher than that of stage I disease (48.7). ALDH1-score positive cases seemed to be associated with a poorer survival according to a survival curve (p = 0.06). CD133 positive cases were significantly associated with a poorer survival according to a survival curve (p<0.01), although there were no relationship between CD133 expression and ALDH1-score. [Conclusion] ALDH1 and CD133 can act as a prognostic marker for stem cells in human lung adenocarcinoma. To determine the ALDH1 and CD133 expression in human lung adenocarcinoma is helpful for targeted therapies against stem cells. Citation Format: Takeaki Miyata, Takashi Yoshimatsu, Atsushi Sekimura, Tetsuya So, Naohiro Nose, Tsunehiro Oyama, Hisao Nagaya, Akinobu Gotoh, Takeaki Miyata, Tsunehiro Oyama. Cancer stem cell markers (ALDH1 and CD133) expression could be associated with a poor prognosis in the patients with lung adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3353.

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