Prognostic significance of HER-2/neu oncoprotein expression in node-positive breast cancer. The influence of the pattern of immunostaining and adjuvant therapy.

BACKGROUND

The influence of HER-2/neu on prognosis of breast cancer is controversial. The authors investigated by immunohistochemistry in node-positive disease the influence of the pattern of immunostaining (membranous or cytoplasmic) on outcome and the prognostic significance of this marker in patients receiving or not receiving adjuvant therapy.

METHODS

The immunostaining for HER-2/neu oncoprotein was performed on formaldehyde-solution-fixed, paraffin-embedded sections of 888 node-positive breast cancers resected between 1980 and 1986 and for which a follow-up of 2.5-10.5 years was available. The staining was performed using a polyclonal antibody (dilution, 1/15).

RESULTS

One hundred forty-three cases (16.1%) revealed a positive membrane staining with or without additional cytoplasmic contribution, whereas cytoplasmic staining alone was noted in 118 cases (13.3%). Positive membrane staining was correlated with more involved lymph nodes (P = 0.005), aneuploidy (P = 0.002), poor nuclear (P < 0.0001) and histologic (P = 0.007) grades, absence of estrogen (P < 0.0001) and progesterone (P < 0.0001) receptor content, and cathepsin D expression (P = 0.009). No relation was found (P > 0.05) with either age, tumor size, or HSP27 expression. Membrane staining was strongly associated with poor distant metastasis-free or overall survival rate (P < 0.0001), whereas cytoplasmic staining had no prognostic significance. Two hundred thirty-two patients (26.1%) received no additional treatment after surgery. The difference in survival rates between cases with positive and negative staining was only significant among patients submitted to adjuvant chemotherapy or hormone therapy.

CONCLUSIONS

This study strongly supports the association of HER-2/neu oncoprotein expression with poor prognosis in node-positive breast cancer and demonstrates that membranous but not cytoplasmic staining is prognostically relevant. It also shows that HER-2/neu oncoprotein expression is useful in predicting survival time only in patients receiving adjuvant therapy, thus suggesting that it may be a marker of drug resistance.