Immunohistochemical staining of estrogen and progesterone receptors: aspects for evaluating positivity and defining the cutpoints.

BACKGROUND: Estrogen (ER) and progesterone (PgR) receptors are predictive and prognostic factors in breast cancer. The most suitable immunohistochemical cutpoints for dividing the tumors in hormone receptor-negatives and -positives may, however, need more consideration. We examined the association between breast cancer survival and cutpoints assessed by four different models. We looked for evidence for which patient subgroups could be handled best through applying different cutpoints. MATERIALS AND METHODS: Three hundred and twenty-four samples of invasive breast cancer were immunohistochemically stained for ER and PgR, bcl-2 and erbB2. Fractions of ER- and PgR-positive cells and also ER and PgR staining scores were assessed. The fractions of stained cells and staining scores, respectively, were determined on the whole section area, and the area of most intense staining. Candidate cutpoints, dividing the patients into good and poor prognosis groups, were tested among all patients group, N+ and N- groups, premenopausal and postmenopausal patient groups. The correlation between immunohistochemistry results of ER, PgR, bcl-2 and erbB2 as well as SMI (standardized mitotic index), patient age, tumor size and axillary lymph node status were tested. RESULTS: The ER score was correlated with age, SMI and bcl-2 positivity. The PgR score was correlated with erbB2 and bcl-2. Lobular carcinomas had higher staining scores of ER and PgR than ductal carcinomas. CONCLUSION: In this material, ER was correlated with factors reflecting the differentiation of the tumor. On the basis of the ER and PgR immunohistochemistry cutpoint analysis, we found that the optimal cutpoints in different patient groups may not be the same.

Quantitation of erbB2 positivity for evaluation of high-risk patients.

BACKGROUND: Because trastuzumab therapy is expected to be effective in a large fraction of erbB2 (HER-2/neu) overexpressing breast cancers, it is important to find the optimal method for evaluation of erbB2 positivity, and the patient group at greatest risk of dying without this therapy. AIM: We evaluated erbB2 immunopositivity in breast cancer with the aim of finding a high-risk group for primary trastuzumab therapy. METHODS: Three hundred and seventeen samples were evaluated with an immunostaining index. Optimal cut point was systematically tested, and the effect of bcl-2 status on survival in the high-risk group was studied. RESULTS: Among N+ patients the index value 1.5 reflected the biggest difference in survival. There was a significant correlation between erbB2 positivity and bcl-2 negativity. ErbB2 was a prognosticator among postmenopausal, N+, and postmenopausal N+ patients. In multivariate analysis, erbB2 was the best prognosticator among postmenopausal N+ patients. Six out of seven N+ patients with erbB2 index 1.5 or above died including all postmenopausal patients. Bcl-2 positivity was associated with longer survival in the erbB2 positive patient group. CONCLUSIONS: The most obvious patients for primary trastuzumab therapy in breast cancer are N+ patients with high erbB2 immunostaining index (> 1.5) and bcl-2 negative immunostaining. In our material 2% of all breast cancer patients fell in this category. This patient group should be selected for testing trastuzumab in the primary treatment.