High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis.
BACKGROUND
Syndecan-1 is a transmembrane heparan sulphate proteoglycan that is involved in cell-cell adhesion, organization of cell-matrix adhesion, and regulation of growth factor signaling.


METHODS
Specimens from 254 consecutive breast carcinoma (BC) cases (110 N0, 144 N1/2) with long-term follow-up (median, 95 months) were immunostained for syndecan-1, estrogen receptor (ER), progesterone receptor (PgR), and p53; in 154 cases, c-erbB-2 status was known. Syndecan-1 mRNA and protein expression also were evaluated in 20 breast tissue samples (10 normal and tumor pairs).


RESULTS
Syndecan-1 was expressed at high levels in 106 (42%) BCs; syndecan-1 up-regulation was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) studies. High syndecan-1 expression was associated with high histologic grade, large tumor size, high mitotic count, c-erbB-2 overexpression, and ER and PgR negative status. At univariate survival analysis syndecan overexpression was related to poor prognosis (P < 0.01 for both overall survival (OS) and disease-free survival). Bivariate survival analysis showed an additive adverse effect for syndecan-1 and c-erbB-2 overexpression. At multivariate analysis, syndecan-1 overexpression was independently associated with poor OS (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.08-2.69). High syndecan-1 expression also was of independent prognostic value for OS in the group of 102 ER-negative patients (HR, 2.42; 95% CI, 1.21-4.82). Stratifying patients on the basis of the type of adjuvant therapy given, high syndecan-1 expression was associated with a higher risk of death only in patients treated with the cyclophosphamide-methotrexate-fluorouracil regimen (HR, 1.9; P = 0.09); at multivariate analysis for OS, this association proved to be of independent statistical significance (P = 0.03; HR, 2.15).


CONCLUSIONS
Syndecan-1 is expressed at high levels in a significant percentage of breast carcinomas and is related to an aggressive phenotype and poor clinical behavior.
Barbareschi
Mattia
M
Department of Pathology, Santa Chiara Hospital, Trento, Italy.
Maisonneuve
Patrick
P
Aldovini
Daniela
D
Cangi
Maria Giulia
MG
Pecciarini
Lorenza
L
Angelo Mauri
Francesco
F
Veronese
Silvio
S
Caffo
Orazio
O
Lucenti
Antonio
A
Palma
Paolo Dalla
PD
Galligioni
Enzo
E
Doglioni
Claudio
C
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology; D015996:Survival Rate; D053668:Syndecan-1; D053667:Syndecans
D000970:Antineoplastic Agents; D017931:DNA Primers; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human