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Overexpression of h-prune in Breast Cancer is Correlated with Advanced Disease Status

¹ Telethon Institute of Genetics and Medicine, Naples, Italy; ² Istituto Anatomia Patologica, Università di Sassari; ³ Istituto di Chimica Biomolecolare-Sezione di Sassari, Consiglio Nazionale delle Ricerche, Località Tramariglio; ⁴ Centro Multizonale di Osservazione Epidemiologica,Azienda U.S.L.1, Sassari, Italy; ⁵ Ospedale San Raffaele, HSR, Departimento di Patologia, Milan, Italy; and ⁶ Centro di ricerca per l'ingegneria genetica di Napoli, Naples., Italy

Requests for reprints: Massimo Zollo, Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy. Phone: 39-081-6132218; Fax: 39-081-6132351; E-mail: zollo{at}tigem.it.

Purpose: 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.

Experimental Design: 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.

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