Overexpression of SLC1a5 in lymph node metastases outperforms assessment in the primary as a negative prognosticator in non-small cell lung cancer

• Published in: Pathology Vol. 50; no. 3; pp. 269 - 275
• Main Authors: Csanadi, Agnes, Oser, Annika, Aumann, Konrad, Gumpp, Vera, Rawluk, Justyna, Nestle, Ursula, Kayser, Claudia, Wiesemann, Sebastian, Werner, Martin, Kayser, Gian
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.04.2018
• Subjects: Adult; Aged; Aged, 80 and over; Amino Acid Transport System ASC - biosynthesis; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Female; glutamine metabolism; Humans; immunohistochemistry; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymphatic Metastasis - pathology; Male; Middle Aged; Minor Histocompatibility Antigens - biosynthesis; Prognosis; Proportional Hazards Models; Retrospective Studies; SLC1a5; survival; glutamine metabolism; SLC1a5; immunohistochemistry; Lung cancer; survival
• ISSN: 0031-3025; 1465-3931
• DOI: 10.1016/j.pathol.2017.10.016

Despite recent advances in therapeutic options, lung cancer is the leading cause of death among malignant diseases worldwide. Glutamine-dependence is an established attribute in cancer tissue with emerging importance as a diagnostic and therapeutic target. We analysed the expression of SLC1a5, a major glutamine transporter, in the primary tumour and corresponding nodal metastasis of non-small cell lung cancer (NSCLC) to investigate its biological impact. Expression of SLC1a5 was analysed by immunohistochemistry in 259 NSCLC and in 142 nodal metastases and correlated with clinicopathological parameters including overall survival. SLC1a5 expression in the primary tumour and in the corresponding lymph node metastasis revealed a positive correlation (p = 0.005). Moreover, overexpression of SLC1a5 was found to be an independent prognostic factor (p = 0.027) if assessed in lymph node metastases only. SLC1A5 expression was studied for the first time in both primary NSCLC and its corresponding nodal metastasis. Our results indicate that overexpression of SLC1a5 is associated with shorter overall survival. This proved to be an independent prognosticator if assessed in the lymph node metastases. Thus, diagnostics in lymph node metastasis provide superior prognostic information for SLC1a5 overexpression and may open target prediction for future therapeutic options.