Markku Helle

Evaluation of cell proliferation in breast carcinoma. Comparison of Ki-67 immunohistochemical study, DNA flow cytometric analysis, and mitotic count

Growth kinetics of 102 breast carcinomas were studied by immunohistochemical analysis with the monoclonal antibody Ki‐67, which reacts with a nuclear antigen in proliferating cells. The results were correlated with ploidy and S‐phase fraction (SPF) analyzed by DNA flow cytometric study and with mitotic count analyzed by light microscopic study. The proportion of Ki‐67‐positive cells (Ki‐67 score) in breast carcinomas varied from 0.6% to 80% (median, 6.3%). Ki‐67 scores were significantly higher in the DNA aneuploid than in the DNA diploid tumors. Ki‐67 scores correlated significantly with tumor SPF in DNA aneuploid tumors. In DNA diploid tumors SPF showed no correlation with Ki‐67 score. High Ki‐67 scores were associated with high mitotic counts (P < 0.0001) and histologic grade (P < 0.0001). Nuclear pleomorphism, tubule formation, or lymph node status were not correlated with Ki‐67 score. In conclusion, Ki‐67 immunostaining correlates with other measures of cell proliferation (SPF, mitotic count) supporting its clinical significance.

Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and dna flow cytometry

Human breast carcinomas (n = 232) were evaluated for estrogen and progesterone receptors (ER, PR) by immunohistochemical study and by cytosol steroid‐binding assay (n = 185). The staining was scored (histoscore) by estimates of relative nuclear staining intensity and the percentage of positively stained carcinoma cells. Of the invasive ductal carcinomas 72% were ER‐positive and 55% were PR‐positive. The invasive lobular, intraductal, tubular, and mucinous carcinomas were the most frequent ER‐positive tumor types, whereas comedo and medullary carcinomas only rarely contained ER. Progesterone receptor was most frequently present in intraductal, tubular, and mucinous carcinomas. Better differentiated tumors with lower histologic grade were significantly associated with high prevalence of immunohistochemically determined ER and PR (P < 0.0001). Proliferative cell fraction, determined by DNA flow cytometric study (n = 63), was inversely related to ER (P = 0.03) and PR (P = 0.05) status. Aneuploidy was independent of ER or PR content.

Reactivity of a monoclonal antibody recognicing an estrogen receptor regulated glycoprotein in relation to lectin histochemistry in breast cancer

We have raised monoclonal antibodies against human milk fat globule membrane antigens and previously shown that one of them, called III D 5, recognises a glycoprotein associated with estrogen receptor activity of breast cancer. In immunoblotting it was shown that the molecule in human milk exclusively stained with III D 5 also binds peanut agglutinin (PNA) and Ricinus communis. In this study we correlate the staining of III D 5 and binding of lectins to tissue sections fixed in formalin and embedded in paraffin. Similar rections were seen only with III D 5 and PNA. Our results suggest that III D 5 and PNA detect overlapping antigenic epitopes in mammary carcinoma. This is in keeping with previous results that PNA or III D 5 reactivity is correlated with estrogen receptor status of breast cancer.

Human milk fat globule antigen III D 5, steroid receptors and histopathologic parameters in breast cancer

Immunohistochemical reactivity of mammary carcinomas with the monoclonal human milk fat globule (HMFG) antibody III D 5, and the estrogen receptor (ER) and progesterone receptor (PR) status were compared with the histopathology of primary breast cancer. The reactivity with HI D 5 has earlier been shown to be associated with the estrogen receptor status of tumours and with a favourable prognisis. The reactivity of tumours with III D 5, as well as the presence of ER and PR correlated significantly with the histological features of differentiation; histological grade, nuclear grade, tumour necrosis and lymphoid infiltration. Reactivity with III D 5 correlated with all these parameters, while the presence of ER did not correlate with the nuclear grade and that of PR correlated only with the nuclear grade and the lymphoid infiltration of tumours. Reactivity of III D 5 may thus have prognostic and therapeutic implications in the management of breast cancer.

Oestrogen receptor content and cancer cell/stroma ratio in mammary carcinoma

In a study of 86 human brest cancers the volume fraction of the neoplastic epithelium was estimated semiquantitatively and a significant association was found between the oestrogen receptor (ER) content and volume fraction of cancer cells of tumours (p < 0.00001). Tumours with very low cellularity could thus be falsely ER negative. When quantitative ER concentration is used to predict the response of tumours to hormonal therapy the cellularity of tumours should be taken in consideration. The cellularity was not related to ER positivity. Although a correlation was seen between the contents of oestrogen and progesterone (PR) receptors, no correlation between PR content and volume fraction of the neoplastic epithelium was observed.

Relationship of the Estrogen Receptor Activation to the Histological Findings in Mammary Carcinoma

The morphological classifications of breast carcinomas have been inadequate in the assessment of response to the therapy or the prognosis of patients. Since the demonstration of a correlation of the estrogen receptor (ER) and the progesterone receptor (PR) status to the response to endocrine therapy (Muire 1975), disease free interval and survival (Knight et al. 1977; Blarney et al. 1980) in breast cancer, attempts have been made to find correlations between the ER and PR status and the histology of breast carcinomas (review, Underwood 1983).