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BMC Cancer. 2012; 12: 106.
Published online Mar 22, 2012. doi:  10.1186/1471-2407-12-106
PMCID: PMC3362775
Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis
Andrea Malfettone,1 Concetta Saponaro,1 Angelo Paradiso,2 Giovanni Simone,#3 and Annita Mangiacorresponding author#1
1Functional Biomorphology Laboratory, National Cancer Centre, Viale Orazio Flacco, 65-70124 Bari, Italy
2Scientific Direction, National Cancer Centre, Viale Orazio Flacco, 65-70124 Bari, Italy
3Pathology Department, National Cancer Centre, Viale Orazio Flacco, 65-70124 Bari, Italy
corresponding authorCorresponding author.
#Contributed equally.
Andrea Malfettone: a.malfettone/at/gmail.com; Concetta Saponaro: titasap/at/hotmail.com; Angelo Paradiso: a.paradiso/at/oncologico.bari.it; Giovanni Simone: g.simone/at/oncologico.bari.it; Annita Mangia: a.mangia/at/oncologico.bari.it
Received August 30, 2011; Accepted March 22, 2012.
Abstract
Background
Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2.
Methods
We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index.
Results
Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level.
Conclusions
The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors.
Keywords: NHERF1, Peritumoral Vascular Invasion, Histological grade, Breast cancer, VEGFR1, Nottingham Prognostic Index
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