Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance

Abstract

By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease-free survival. This influence of DNA content on disease-free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more tumor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors.