Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.
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.
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011233:Precipitin Tests; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human