Intratumoral heterogeneity in primary breast carcinoma: study of concurrent parameters

Intratumoral heterogeneity for prognostic factors (ploidy, proliferation, hormone receptor positivity) has been demonstrated in primary breast carcinoma by both flow cytometric and image analysis methods. Previously, heterogeneity in tumors had been demonstrated for only singular parameters. Our objective, using maps of tumors in which discrete regions can be analyzed simultaneously for DNA index (DI) and proliferative activity, was to demonstrate heterogeneity with respect to two parameters and to determine whether any interparametric relationships existed.

We analyzed 25 cases of archived, paraffin-embedded breast carcinoma (ductal) for Feulgen stain DNA analysis and MIB-1 immunohistochemistry using the CAS 200 Image Cytometer. For each tumor, four discrete regions were analyzed including tumor-host tissue interface sectors.

Of 25 cases, 19 (76%) were homogeneously diploid or near-diploid aneuploid, and 6 (24%) were heterogeneous. Within the heterogeneous group, all cases had at least one diploid and one or more aneuploid populations from separate discrete regions. Five of six DI heterogeneous tumors displayed diploid values for the overall measurements of the respective tumors, based on analysis of 200 or more nuclei. Eight of 25 cases (32%) showed significant measurable variation for MIB-1 proliferative activity in various sectors of tumor. All the MIB-1 heterogeneous tumors, with one exception, were homogeneously diploid.

These findings demonstrate that (1) heterogeneity is present with respect to DI and proliferative activity in breast carcinoma and is relatively common, (2) tumors homogeneous for one parameter may be heterogeneous for another, and (3) heterogeneity for proliferative activity is more common in homogeneously diploid tumors than in heterogeneous/aneuploid tumors.