Reduced expression of &#x03B1;-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Serena Bonin; Alessia Parascandolo; Cinzia Aversa; Renzo Barbazza; Nobuo Tsuchida; Maria Domenica Castellone; Giorgio Stanta; Giancarlo Vecchio

doi:10.18632/oncotarget.24445

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Research Papers:

Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Serena Bonin, Alessia Parascandolo, Cinzia Aversa, Renzo Barbazza, Nobuo Tsuchida, Maria Domenica Castellone, Giorgio Stanta and Giancarlo Vecchio _

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Oncotarget. 2018; 9:15228-15238. https://doi.org/10.18632/oncotarget.24445

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Abstract

Serena Bonin1,*, Alessia Parascandolo2,*, Cinzia Aversa1, Renzo Barbazza1, Nobuo Tsuchida3, Maria Domenica Castellone4, Giorgio Stanta1 and Giancarlo Vecchio5,6,7

1Dipartimento di Scienze Mediche, Università di Trieste-Cattinara, Trieste, Italy

2IRCSS SDN, Naples, Italy

3Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

4Istituto di Endocrinologia e Oncologia Sperimentale G.Salvatore, CNR, Naples, Italy

5Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy

6Istituto Superiore di Oncologia, Naples, Italy

7Istituto Superiore di Oncologia, Genoa, Italy

*Co-first authors

Correspondence to:

Giancarlo Vecchio, email: [email protected]

Keywords: breast cancer; luminal B; lymph node metastasis; α-L-Fucosidase-1; immunohistochemistry

Received: October 06, 2017 Accepted: February 01, 2018 Epub: February 07, 2018 Published: March 16, 2018

ABSTRACT

Background: The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases.

Results: Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness.

Conclusions: This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival.

Methods: We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

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Research Papers:

Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Abstract