Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis.
OBJECTIVE
The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas.


METHODS
CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization.


RESULTS
In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with 'basal-like' immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression.


CONCLUSIONS
The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.
Savage
Kay
K
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
Lambros
Maryou B K
MB
Robertson
David
D
Jones
Robin L
RL
Jones
Chris
C
Mackay
Alan
A
James
Michelle
M
Hornick
Jason L
JL
Pereira
Emilio M
EM
Milanezi
Fernanda
F
Fletcher
Christopher D M
CD
Schmitt
Fernando C
FC
Ashworth
Alan
A
Reis-Filho
Jorge S
JS
D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D051242:Caveolin 1 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D016896:Treatment Outcome
D051242:Caveolin 1