HMGA1 protein expression in familial breast carcinoma patients.
HMGA protein overexpression is associated with a highly malignant phenotype and it is also causally related to neoplastic cell transformation. Our previous results have shown that HMGA1 was not expressed in normal breast tissue whereas HMGA1 staining was intense in 25% of hyperplastic lesions with cellular atypia and in 60% of sporadic ductal carcinomas. Moreover, HMGA1 protein levels were significantly correlated with c-Erb-B2 expression. These results suggested HMGA1 expression as a novel prognostic factor in breast ductal carcinomas. In order to investigate whether the HMGA1 detection might have a prognostic role also for inherited breast carcinomas we have analysed the expression of the HMGA1 proteins in 116 breast familial carcinomas associated with BRCA1 or BRCA2 or negative for mutations in both genes (BRCAX). HMGA1 expression was weakly positive in 23 (20%), moderately positive in 34 (29%) and strongly positive in 20 (17%) breast carcinomas, and was not detected in 39 of them (34%). Statistical analysis of the immunostaining data showed that HMGA1 was significantly overexpressed, with a more intense staining, in BRCA2 (p=0.0009) and BRCAX (p=0.0134) patients compared to BRCA1 ones. Furthermore, in BRCA2 positive patients, the expression of HMGA1 seems to correlate with a favourable prognosis with a median overall survival of 65 months and a 5-year survival rate of 80% for HMGA1-negative patients, while median overall survival in the HMGA1-positive subsets was not reached with 5-year survival rates ranging from 84% to 100% of patients (p=0.0198). Conversely, no correlation was found between HMGA1 expression and overall survival in patients carrying inherited mutations in the BRCA1 and in BRCAX patients.
Chiappetta
Gennaro
G
Istituto Nazionale dei Tumori, Fondazione Pascale, 80131 Naples, Italy. chiappetta.osd@fondazionepascale.it
Ottaiano
Alessandro
A
Vuttariello
Emilia
E
Monaco
Mario
M
Galdiero
Francesca
F
Gallipoli
Adolfo
A
Pilotti
Silvana
S
Jodice
Giovanna
G
Siranoush
Manoukian
M
Colombo
Mara
M
Ripamonti
Carla B
CB
Pallante
Pier Lorenzo
PL
Radice
Paolo
P
Fusco
Alfredo
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D025741:HMGA1a Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010375:Pedigree; D055815:Young Adult
D009363:Neoplasm Proteins; D025741:HMGA1a Protein