Overexpression of h-prune in breast cancer is correlated with advanced disease status.
OBJECTIVE
The h-prune gene is involved in cellular motility and metastasis formation in breast cancer through interacting with the nm23-H1 protein. The aim of this study was to better define the clinical and pathologic role of h-prune in breast cancer patients.


METHODS
Using immunohistochemistry, we assessed h-prune and nm23-H1 protein expression in two series of breast cancer patients: (i) in 2,109 cases with pathologic reports on primary tumors and (ii) in 412 cases with detailed clinical information. To assess the role of DNA amplification in gene activation, the h-prune copy number was evaluated by fluorescence in situ hybridization analysis in 1,016 breast cancer cases.


RESULTS
In the patients tested (n = 2,463), 1,340 (54%) had an increased level of h-prune expression; a positive immunostaining for nm23-H1 was observed in 615 of 2,061 (30%) cases. Overexpression of h-prune was associated with multiple gene copy number at chromosome 1q21.3 in a very limited fraction of cases (68 of 1,016; 6.7%), strongly indicating that alternative pathways induce h-prune activation in breast cancer. Multivariate Cox regression analysis showed that neither h-prune overexpression nor decreased nm23-H1 immunostaining is independent prognostic factors. However, a significant association of h-prune overexpression with either advanced lymph node status (P = 0.017) or presence of distant metastases (P = 0.029) was observed.


CONCLUSIONS
Although not significantly correlated with overall survival, positive h-prune immunostaining identifies subsets of breast cancer patients with higher tumor aggressiveness. Further investigations using larger collections of advanced breast cancer patients are required for assessing the predictive role of h-prune in breast cancer.
Zollo
Massimo
M
Telethon Institute of Genetics and Medicine, Naples, Italy. zollo@tigem.it
Andrè
Alessandra
A
Cossu
Antonio
A
Sini
Maria C
MC
D'Angelo
Anna
A
Marino
Natascia
N
Budroni
Mario
M
Tanda
Francesco
F
Arrigoni
Gianluigi
G
Palmieri
Giuseppe
G
D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D015331:Cohort Studies; D004247:DNA / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases; D016016:Proportional Hazards Models; D012044:Regression Analysis; D013997:Time Factors
D002352:Carrier Proteins; D004247:DNA; C438732:PRUNE1 protein, human; D010744:Phosphoric Monoester Hydrolases