Abstract. Background/Aim: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCsDespite continuous efforts to improve therapeutic response, lung cancer is the most common cause of cancer-related deaths in Japan, with adenocarcinoma by far the most common histology, accounting for nearly 70% of lung cancer cases (1). Cancer stem cells (CSCs) have the ability for selfrenewal and multipotently differentiate (2). CSCs may be highly resistant to chemotherapy and radiation, and be responsible for tumor initiation, progression and metastasis (3, 4). Accumulating evidence supports the existence of a CSC phenotype in human lung cancer (3, 5-7). The metabolic marker aldehyde dehydrogenase isoform 1A1 (ALDH1A1) and the cell-surface marker CD133 are reported to be markers of lung CSCs (3). We, therefore, investigated ALDH1A1 and CD133 expression in a retrospective cohort of 92 patients with lung adenocarcinoma. The objectives were to determine the association between ALDH1A1 and CD133 expression in lung adenocarcinoma, the relationship between their expression and the clinichopathological parameters, and the prognostic value of ALDH1A1 and CD133. Materials and MethodsPatient population and clinicopathological data. We examined a series of 154 Japanese patients with lung adenocarcinoma who underwent surgical treatment at Fukuoka-Wajiro Hospital, Fukuoka, Japan from 2006-2012. Ninety-two out of 154 (59.7%) patients were selected based on the following inclusion criteria: (i) no chemotherapy or radiotherapy before surgery, and (ii) the availability of an adequate paraffin block and clinicopathological data for the analysis. Follow-up information was obtained from the patients' records. Routinely collected clinicopathological data included age, gender, smoking history and pathological stage. There were 49 males (53%) and 43 females (47%), with a median age of 71 years (range=40-92 years) at the time of surgery; 43 (47%) patients were <70 years and 49 (53%) were ≥70 years of age. Half of the patients (n=46) had a smoking history. The pathological stages were: stage I, n=62 (67.4%); stage II, n=14 (15.2%); stage III, n=12 (13.0%); and stage IV, n=4 (4.4%) (TNM staging of lung cancer) (8). The median follow-up period was 1,702 days (range=4-3679 days). Recurrence was diagnosed by computed tomography alone or combined with positron-emission tomography.

a b s t r a c tPurpose: Lung cancer is responsible for most cancer-related deaths. There are two broad types of lung tumors, usually classified as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Current clinicopathological staging systems provide the advantage of standardized criteria for assessing tumor stage, and a relationship between advancing tumor stage and poor prognosis has been established for NSCLC. However, these staging systems have not led to clear criteria for selection of therapy for individual patients with NSCLC. The concept of therapy based on anatomical location, as used in staging systems, is poorly associated with the cancer stem cell (CSC) characteristics of individual tumor tissues. CSCs may have self-renewal and multipotent differentiation abilities and be responsible for tumor initiation, progression, and metastasis; they are highly resistant to chemoradiotherapy. Therefore, research into CSCs will provide the basis for developing of novel diagnostic and therapeutic strategies. We review aldehyde dehydrogenase isoform 1 (ALDH1), CD133, CD44 and CD166 as CSC markers, as weel as the Wnt/b-catenin pathway, KRAS, and the embryonic stem cell (ESC) signature. Study selection: PubMed databases were searched for relevant articles. Results: The positivity rate for ALDH1 immunohistochemical (IHC) staining is 19% in patients with stage I NSCLC [1]. The positivity rates for CD133 are 19e48.9% [2e4] and for CD44 are 50.4e67.3% in patients with NSCLC [5,6]. Conclusions: CSCs have been identified in lung cancer and will provide new therapeutic targets for lung cancer. Research on these cells could improve the prognosis of lung cancer.

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