Correlation between cytometric features and mitotic frequency in human breast carcinoma

Abstract

An evaluation of cytometric features of 142 human breast cancers was performed. Twenty-two cytometric features describing density, structure and shape were correlated with mitotic frequency and labeling index of some of the tumors and with the observed recurrence rate of the tumors within 3 years after removal of the breast. A new cytometric measure was also created by combining the four features most strongly correlated with mitotic frequency of the tumors. It was found that the variance of the nuclear area was the feature that was most strongly correlated with mitotic frequency and recurrence rate. No new cytometric measure created by combining the four features most strongly correlated with mitotic frequency, correlated as well as variance of nuclear area even though the four features were optimized by multiple regression analysis for their correlation with mitotic frequency.Key terms: Breast cancer, mitotic frequency, cytometric features One of the important components of cytometric work in cancer diagnosis is the evaluation of features (13) and their correlation to other biologically important factors. Surprisingly little has been accomplished in the field of feature evaluation although more than 20 years ago several groups using different modes of spectrophotometry in visible light began to pursue DNA determinations in tumor materials. Although abnormal DNA distribution patterns were noted in most human tumors few or no attempts have been made to "grade" these abnormal patterns or to relate them to other observations such as mitotic frequency or patient survival rather than conventional morphology. In many tumors, including breast carcinoma, the mitotic frequency and/or labeling index after incubation with tritiated thymidine are expressions of DNA-synthesis activity.In a study of the possible correlations between morphologic and epidemiologic characteristics of breast cancer we have developed a method of cytometric characterization of tumor cell nuclei populations (14). This method had a comparatively high reproducibility and consistency.In the present study the various morphometric features of I Supported by NIH/NCI Contract NOlCB53968.the nuclei populations of breast carcinoma are correlated with mitotic frequency of the tumors and in one sample of the populations also with the labeling index.Materials and Methods Determination of Cytometric Features: The cytometric features were obtained from the tumors of I42 breast cancer patients. After removal each specimen was taken directly to the laboratory. Cells were aspirated from the tumor with a 22-gauge needle and a 20-ml syringe in a syringe holder. This method produces a proportion of single dispersed cells that are well-suited to cytometric studies. The cytologic specimens were fixed immediately in fresh Carnoy's solution and stained with chrome-alum gallocyanin (3, 4). One hundred nuclei from each specimen were recorded. Randomly selected undamaged epithelial cells were chosen for recording.A diode array scanner coupled with a light microscope was used...

Predicting breast cancer recurrence

“…",'~More recently, it has been shown that malignant tumors have abnormal DNA level^.^^.^^ It has also been shown that abnormal DNA distribution is correlated with recurrence risk and mitotic frequency. 20 The degree of aneuploidy seems to be an important variable during the whole follow-up period, expressed either as mitotic frequency or variance of DNA content among tumor cell nuclei. These two variables are closely corDifferentiation of the tumor seems to play its main role during the early follow-up period.…”

“…We were able to clearly demonstrate that some of these cytometric characteristics are correlated with the mitotic activity in the tumor. 20 Diflerentiation: Some studies have shown that tumor differentiation has a predictive value in the diagnosis of breast can~er.~.~~-*'The degree of differentiation of breast cancer is expressed by the tendency of cancer cells to dissociate when a fine-needle biopsy of the tumor is performed. We have recently described a method of expressing this dissociation in quantitative, morphometric terms, i.e., a quantitative measure of tumor differentiat i~n .~' Essentially, the tumor differentiation in that study was expressed as the average size of clusters in epithelial nuclei after division by the mean nuclear area.…”

Advances in Formal Pathogenesis: Allometry and Allied Comparative Methods of Stereology for Recognizing Relative Growth in Proliferative Lesions

“…Of several cytometric variables examined through multiple regression analysis, vari ance of nuclear area was the variable most strongly correlated with the mitotic density in cases of human breast carcinoma [5]. The mitotic index of 20 cases of minute colonic carcinoma experimentally induced in rats was greater in differentiated than in undif ferentiated tumors.…”

Method for counting mitoses by image processing in feulgen stained breast cancer sections

“…The number of mitoses seen in tissue sections is an important factor in grading many malignancies, especially for the prognosis of breast, ovarian, and other tumors (1, 20,22,29). Also, mitotic activity is a method to evaluate the rate of proliferation of tumors.…”