Elsevier

Lung Cancer

Volume 84, Issue 1, April 2014, Pages 73-78
Lung Cancer

Clinical relevance of galectin-1 expression in non-small cell lung cancer patients

https://doi.org/10.1016/j.lungcan.2014.01.016Get rights and content

Abstract

Background

Identification of biomarkers in lung cancer, a leading cause of cancer-related mortality, has a meaningful clinical relevance in the quest of novel prognostic factors and therapeutic targets. The glycan-binding protein galectin-1 (Gal-1) modulates tumor progression by mediating cell–cell and cell–extracellular matrix interactions, as well as angiogenesis and tumor immune-escape. Previous works reported the expression of Gal-1 in lung cancer, although its clinical significance remains uncertain.

Objective

To assess the clinicopathologic relevance and prognostic value of Gal-1 expression in a cohort of 103 Stage I–III non-small cell lung cancer (NSCLC) patients.

Methods

Gal-1 expression was determined by immunohistochemistry in tumor tissue samples. The percentage of immunoreactive tumor cells and stroma, as well as the presence of blood vessels with positively stained endothelium in the tumor and surrounding normal tissue, were recorded. Results were correlated with the clinicopathologic factors of the patients (Spearman's rank correlation coefficient, chi-square test) and overall survival by univariate (Kaplan Meier) and multivariate analyses (Cox regression hazard model).

Results

We did not observe significant associations between Gal-1 expression and relevant clinicopathologic features at diagnosis of NSCLC. However, Kaplan Meier analysis revealed a significant association between Gal-1 expression and overall survival, when Gal-1 expression was analyzed on tumor cells alone (“tumor cell percentage”) or when an integrated score accounting for tumor cell as well as stromal expression of Gal-1 (“total score”) was assessed. Patients showing high Gal-1 expression evidenced a poorer clinical outcome. Furthermore, “total score” remained significantly associated with survival by multivariate Cox regression analysis in the whole cohort of patients, even when controlling for the classical predictors and prognostic factors of NSCLC.

Conclusion

We conclude that Gal-1 expression may be a useful biomarker for better prediction of the clinical outcome and management of NSCLC patients.

Introduction

Lung cancer is the most frequent and one of the most deadly cancer types. In Argentina, the age-standardized mortality rates were 31.9 among men and 7.5 among women per 100,000 inhabitants per year (1990–2005), being the leading cause of cancer-related death in men and the fourth leading cause in women [1]. Most lung cancers (85%) are NSCLC, which consist of squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Treatment options depend on stage of disease and include surgery, radiation, platinum doublet chemotherapy, and targeted therapies in some cases [2]. The most important prognostic factor for survival is the tumor, node, metastasis (TNM) system, which has been revised in 2009 [3]. Nevertheless, data are still missing with regards to survival and predictive features, as even among patients at early stages of the disease, about 30% relapse and die within 5 years of surgery [4]. A better understanding of the mechanisms leading to adverse clinical outcomes is likely to improve therapeutic intervention of NSCLC patients.

Anti-tumor immune responses play important roles in eradicating and suppressing the growth of several cancer types. However, tumors can evade immune surveillance through a number of immune escape mechanisms and immunosuppressive molecules [5], some of which have served as clinical biomarkers delineating the prognosis of cancer patients (reviewed in [6]). Gal-1 belongs to a family of soluble lectins defined by a common structural fold and a conserved carbohydrate recognition domain that recognizes glycans containing the disaccharide N-acetyllactosamine [7]. Secretion of Gal-1 has been shown to contribute to the immunosuppressive activity of melanoma, Hodgkin's lymphoma and pancreatic carcinoma, suggesting the essential role of this protein in tumor-immune escape by tumors [8], [9], [10]. In lung cancer, several preclinical studies documented a link between Gal-1, immune escape and tumor progression [11], [12]. Furthermore, a prognostic significance of Gal-1 in human lung cancer has been proposed [13], [14].

We undertook this study to provide a detailed retrospective assessment of Gal-1 expression in 103 cases of primary NSCLC Stage I–III and analyzed its clinicopathologic role and prognostic significance. Our results indicate that an integrated score accounting for tumor as well as stromal expression of Gal-1 represents an independent prognostic factor of poor outcome in NSCLC patients.

Section snippets

Patients and tumor specimens

103 samples from patients with NSCLC were obtained from the “Hospital Italiano de Buenos Aires” for this retrospective analysis. Tissue specimens were obtained at surgery from untreated patients, fixed in 4% (v/v) formaldehyde in PBS immediately after removal and embedded in paraffin. The study included white individuals, Curative resections were performed from 1997 through 2009. Staging was determined following the American Joint Committee on Cancer Guidelines, 7th edition [3]. Data on

Gal-1 expression in human NSCLC

Gal-1 was assessed by immunohistochemistry in 103 tissue specimens derived from primary NSCLC. Tumor cells showed positive diffuse or granular staining for Gal-1 that was exclusively cytoplasmic (Fig. 1a). Gal-1 expression was detected in 53/103 (51.5%) NSCLC samples (“tumor cell percentage”). The tumor stroma displayed widespread Gal-1 staining both in stromal cells and the extracellular milieu (Fig. 1c), with 85/103 (82.5%) immunoreactive cases in more than 50% of total tumor stroma (“tumor

Discussion

In this retrospective study, we evaluated Gal-1 expression in tumor cells and stroma of human NSCLC samples to assess whether this information could offer any prognostic value for the management of this cancer type. We report an association between increased Gal-1 expression and decreased overall survival in a cohort of 103 NSCLC patients, after adjustment for other predictors of outcome. This finding may be relevant to guide improved medical treatment and, together with several lines of

Conflict of interest statement

None declared.

Acknowledgements

This work was supported by grants from Argentinean Agency for Promotion of Science and Technology (ANPCyT, PICT 2008-0712 and PICT 2012-2440), Universidad de Buenos Aires (UBA, UBACYT M0243), CONICET and Sales Foundation.

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