ALDH1 and SALL4 Expression in Cell Block Samples from Patients with Lung Adenocarcinoma and Malignant Pleural Effusion.

Tomohiro Kanayama,Yuko Imaizumi,Kei Noguchi,Mikiko Matsuo,Ayumi Niwa,Toshiaki Taniguchi,Tatsuo Kato,Akira Hara,Hiroyuki Tomita,Yuichiro Hatano,Isao Okazaki,Takahiro Kuroda

doi:10.3390/diagnostics11081463

Abstract

Malignant pleural effusion (MPE) can accompany advanced lung adenocarcinoma. Recent studies suggest that MPE could contain a heterogeneous subpopulation of cells with stem-like properties, such as tumorigenicity and self-renewal, indicating that they could be the source of metastasis. Although previous studies analyzed the correlation between cancer stem cell (CSC) marker expression and clinical outcomes using lung cancer tissues, investigations regarding the association of MPE with CSC marker expression are limited. We performed immunohistochemistry to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and Sal-like 4 (SALL4) in 46 cell block samples of MPE from patients with lung adenocarcinoma. ALDH1-positive and SALL4-positive cancer cells in MPE were detected in 30 (65.2%) and 21 samples (45.7%), respectively. Cluster formation was detected in 26 samples (56.5%). The number of clusters was significantly higher in ALDH1-positive/SALL4-negative samples. SALL4 expression was inversely correlated with the cluster ratio (r = −0.356) and positively associated with the Ki-67 index (r = 0.326), suggesting that MPE cells with high SALL4 expression comprised the proliferative subpopulation. In conclusion, we demonstrated that MPE contains an ALDH1-positive/SALL4-negative subpopulation exhibiting cluster formation and a SALL4-positive proliferative subpopulation.

Highlights

Lung adenocarcinoma is the leading cause of cancer mortality globally
Among 78 cases in total, 46 patients were pathologically diagnosed with primary lung adenocarcinoma, and their cell block samples featured Malignant pleural effusion (MPE)
We analyzed the correlation between aldehyde dehydrogenase 1 (ALDH1) and Sal-like 4 (SALL4) expression; no significant correlation was noted (Figure 2). These results suggest that ALDH1 and SALL4 expression is, in part, associated with MPE in human lung adenocarcinoma

Summary

Introduction

Lung adenocarcinoma is the leading cause of cancer mortality globally. Currently available therapies are relatively ineffective, and the age-standardized 5-year survival rate is 10–20% in most countries [1,2]. Treatment failure in patients with lung cancer can be attributed to the presence of a subpopulation of cancer cells with distinctive features, defined as cancer stem cells (CSCs) or cells with stem cell-like properties [3,4,5,6]. As observed in other cancers, CSCs in lung cancer have the ability to generate new tumors by exploiting their stem cell nature, including the ability to self-renew and differentiate into multiple cell lineages [7]. Several specific markers have proven useful for the isolation of subsets enriched for CSCs in lung cancer, including CD133, CD44, and aldehyde dehydrogenase 1 (ALDH1) activity [8]. Inhibition of ALDH activity is expected to effectively eradicate the drug-tolerant CSC subpopulation during lung cancer treatment [14]

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Discussion

Conclusion