Endocrine Abstracts (2006) 11 P235

IGF II protein expression in breast cancer. Relationship with the most important predictive parameters in breast malignancy

EG Giustarini1, AP Pinchera1, DC Campani2, PF Fierabracci1, KC Cullen3 & CG Giani1


1Dipartimento di Endocrinologia e Metabolismo-Università di Pisa, Pisa, Italy; 2Dipartimento di Oncologia-Università di Pisa, Pisa, Italy; 3Lombardi Cancer Research-Georgetown University, Washington DC, United States.


Recent in situ hybridization data showed high content of IGF-II mRNA in the stroma of breast cancer. The aim of this study was to examine the expression of IGF-II protein and its relationship with several prognostic parameters in 75 ductal infiltrating carcinoma (DIC) of the breast.

The tissue sections were evaluated for IGF II protein, proliferating activity, ER, PR, p53, P21 oncogene expression using immunohistochemical procedures. The amoumt of the stromal proliferation was assessed in all cases. The menopausal status, the axillary nodes involvement and the nuclear degree were known.

Thirty-five patients (35/75: 44.3%) were pre-menopausal and 47 (62.6%) had node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (18/75: 24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected in the stroma as well as in the cytoplasm of epithelial cancer cells: marked IGF-II content was found in 12 specimens (12/75: 16.0%), slight in 14 (18.7%) and moderate in 31(41.3%). Twenty-four tumors (24/75: 32.0%) showed high proliferating activity. Both ER and PR were expressed in the nucleus of cancer cells: 49/75 DIC (65.3%) were ER positive (ER+) and 34 (45.3%) PR positive (PR+). p21 protein was detected in 37 tumors (37/75: 49.6%) and p53 in 12 (16%).

IGF-II protein was not related with menopausal status. lymph-node metastases, nuclear grade, proliferating activity, ER and p53 oncogene. In contrast, IGF-II was strongly correlated with stromal proliferatiom (P<0.001), with PR (P:0.04) and with p21 oncogene (P:0.01).

The results of this study demonstrate that in DIC of the breast IGF-II protein is expressed in the epithelium as well as in stroma of the majority of tumors and that it is correlated with stromal amount, with PR and p21 oncogene expression. These findings indicate that in breast cancer, IGF-II expression is connected with the stromal proliferation and with two important regulators of breast cancer growth and differentiation.

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