Neu-Protein Overexpression in Breast Cancer

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.

c-erbB-2 oncogene as a prognostic marker in breast cancer

“…The percentage of tumours expressing the oncogene was consistently in the upper teens or low twenties which is entirely consistent with the results of other published studies using monoclonal or polyclonal antibodies on formalin fixed paraffin embedded sections (Thor et al, 1989;Paik et al, 1990;Walker et al, 1989; Van de Vivjer et al, 1988;Richner et al, 1990).…”

“…Other studies have shown a significant effect of c-erbB-2 expression in the overall survival analysis but not in the recurrence free analysis (Paik et al, 1990;Parkes et al, 1990; Van de Vivjer et al, 1988), but only that by Paik shows c-erbB-2 expression to be independent prognostic significance on multivariate analysis.…”

“…There may however also be some relationship between c-erbB-2 expression and responsiveness to treatment. A number of studies show that the prognostic effect of c-erbB-2 expression is stronger for survival than it is for recurrence (O'Reilly et al, 1991;Gullick et al, 1991;Wright et al, 1989a;Paik et al, 1990;Ro et al, 1989;Parkes et al, 1990;Tsuda et al, 1989;Van de Vivjer et al, 1988). This implies that part of the prognostic effect of c-erbB-2 expression is exerted during the period after recurrence, a period when the patients are likely to be receiving chemo-or hormonal therapy.…”

c-erbB-2 positive breast tumours behave more aggressively in the first years after diagnosis

“…Correlations were found between membrane staining tumours and patho-histological findings such as tumour size (van de Vijver et al, 1988), negative ER-content (De Potter et al, 1989a;Thor et al, 1989;Wright et al, 1989a;Kommoss et al, 1990;De Potter et al, 1990), lymph node involvement (Berger et al, 1988;Thor et al, 1989), histological grade (berger et al, 1988;Barnes et al, 1988;Wright et al, 1989a) and survival time (Thor et al, 1989;Wright et al, 1989a).…”

Treatment of screen detected ductal carcinoma in situ: a silver lining within a grey cloud?

“…In addition, small cell and large cell variants may be distinguished, the latter usually being components of comedo carcinomas, which are most likely to over-express the protooncogene C-erbB-2 (van de Vijver et al, 1988). This introduces heterogeneity into the classification of DCIS and emphasises the need for large studies in order that sub-group analysis may be undertaken, so that invasive diathesis may be quantified.…”