A novel highly reactive Fab antibody for breast cancer tissue diagnostics and staging also discriminates a subset of good prognostic triple-negative breast cancers

Thaise G Araújo; Carlos E Paiva; Rafael M Rocha; Yara C P Maia; Angela A S Sena; Carlos Ueira-Vieira; Ana Paula Carneiro; Juliana F Almeida; Paulo R de Faria; Donizeti W Santos; Luanda Calábria; Tânia M Alcântara; Fernando A Soares; Luiz R Goulart

doi:10.1016/j.canlet.2013.09.029

A novel highly reactive Fab antibody for breast cancer tissue diagnostics and staging also discriminates a subset of good prognostic triple-negative breast cancers

Cancer Lett. 2014 Feb 28;343(2):275-85. doi: 10.1016/j.canlet.2013.09.029. Epub 2013 Oct 4.

Affiliations

¹ Federal University of Uberlandia, Institute of Genetics and Biochemistry, Nanobiotechnology Laboratory, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlandia, MG, Brazil.
² Division of Breast and Gynecological Tumors, Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, SP, Brazil.
³ AC Camargo Cancer Hospital, São Paulo, SP, Brazil.
⁴ Federal University of Uberlandia, Biomedical Sciences Institute, Uberlandia, MG, Brazil.
⁵ Obstetric Division, Internal Medicine, University Hospital, Federal University of Uberlandia, Uberlandia, MG, Brazil.
⁶ Pathology Division, Internal Medicine, University Hospital, Federal University of Uberlandia, Uberlandia, MG, Brazil.
⁷ Federal University of Uberlandia, Institute of Genetics and Biochemistry, Nanobiotechnology Laboratory, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlandia, MG, Brazil; University of California Davis, Dept. of Medical Microbiology and Immunology, Davis, CA, USA. Electronic address: [email protected].

PMID: 24099914
DOI: 10.1016/j.canlet.2013.09.029

Abstract

The discovery of novel markers for breast cancer (BC) has been recently relied on antibody combinatorial libraries and selection through phage display. We constructed a recombinant Fab library, and after selections against BC tissues, the FabC4 clone was thoroughly investigated by immunohistochemistry in 232 patients with long-term follow-up. The FabC4 ligand was determined by mass spectrometry. The FabC4 expression was associated with younger age, lack of progesterone receptor, higher histological grades and non-luminal subtypes, and it also identified a subset of good prognostic triple-negative BCs, possibly targeting a conformational epitope of Cytokeratin-10 (CK10). This new CK10-epitope specific antibody may open new possibilities in diagnostic and therapeutic strategies.

Keywords: Breast cancer; Combinatorial library; Phage display; Recombinant antibody.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Breast Neoplasms / diagnosis*
Disease-Free Survival
Female
Humans
Immunoglobulin Fab Fragments* / genetics
Mass Spectrometry
Microarray Analysis
Middle Aged
Neoplasm Staging
Peptide Library
Prognosis
Triple Negative Breast Neoplasms / diagnosis*

Substances

Immunoglobulin Fab Fragments
Peptide Library