@article {cite-key,
	title = {Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.},
	journal = {N Engl J Med},
	volume = {319},
	number = {19},
	year = {1988},
	month = {Nov},
	pages = {1239{\textendash}1245},
	address = {Department of Pathology, Netherlands Cancer Institute, Amsterdam.},
	abstract = {Amplification of the neu proto-oncogene in breast cancer has been reported to correlate with the presence of lymph-node metastases and with a poor prognosis. We describe a method for the immunohistochemical detection of overexpression of neu protein on formalin-fixed paraffin-embedded tissue, with the use of two different monoclonal antibodies. In a group of tumors with a known neu-gene copy number, intense membrane staining of tumor cells was present in all tumors with neu-gene amplification. Of 189 tumors from patients with Stage II breast cancer, 27 (14 percent) had neu-membrane staining. Neu overexpression was associated with larger tumor size (P = 0.006) but not with lymph-node involvement. Neu-protein expression in lymph-node metastases was the same as its expression in primary tumors. Among the patients with neu overexpression (median follow-up, 37 months), disease-free survival was not significantly shorter; overall survival was reduced significantly in these patients (P = 0.042), but this reduction did not remain significant after adjustment for tumor size. Of 45 ductal carcinomas in situ, 19 (42 percent) had neu-membrane staining. These 19 were all of the large-cell, comedo growth type. None of 16 ductal carcinomas in situ of small-cell, papillary, or cribriform growth type had neu overexpression. We conclude that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but we could find no association of overexpression with lymph-node status or tumor recurrence.},
	issn = {0028-4793 (Print); 0028-4793 (Linking)},
	doi = {10.1056/NEJM198811103191902},
	author = {Van de Vijver, M J and Peterse, J L and Mooi, W J and Wisman, P and Lomans, J and Dalesio, O and Nusse, R}
}
