Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer.
In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.
Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Kiel, Germany. antonia.wenners@uk-sh.de
Antonia Sophie
AS
Wenners
Keyur
K
Mehta
Sibylle
S
Loibl
Hyerim
H
Park
Berit
B
Mueller
Norbert
N
Arnold
Sigrid
S
Hamann
Joerg
J
Weimer
Beyhan
B
Ataseven
Silvia
S
Darb-Esfahani
Christian
C
Schem
Christoph
C
Mundhenke
Fariba
F
Khandan
Christoph
C
Thomssen
Walter
W
Jonat
Hans-Juergen
HJ
Holzhausen
Gunther
G
von Minckwitz
Carsten
C
Denkert
Maret
M
Bauer
D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012074:Remission Induction; D046888:Tissue Array Analysis / Q000706:statistics & numerical data; D016896:Treatment Outcome
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C489506:LCN2 protein, human