COMPARATIVE-ASSESSMENT OF PROLIFERATION AND DNA CONTENT IN BREAST-CARCINOMA BY IMAGE-ANALYSIS AND FLOW-CYTOMETRY

  • 1 May 1990
    • journal article
    • research article
    • Vol. 136  (5) , 1115-1124
Abstract
Although tumor DNA content and proliferation are usually determined by flow cytometry (FCM), quantitative microsopic image analysis is a viable alternative technique that also provides important histologic correlations. To compare these methods, we measured DNA content and proliferation in 54 consecutive breast cancers and 15 benign breast lesions by FCM and IA. DNA content determination was concordant in 49 of 54 cancers measured by FCM and IA. Four of the discordant cases were aneuploid by IA and diploid by FCM. There was good correlation between the DNA index (DI) measured by FCM and IA (r = 0.89, P < 0.0001). Proliferation was assessed by IA quantitation of Ki-67 and PCN/Cyclin antibody staining, as well as by flow cytometric S-phase fraction (SPF). Ki-67 positivity was greater in breast cancer than in benign controls (21.6% .+-. 13.1% vs. 7.9% .+-. 5.6% [P < 0.0001]), as was PCNA/Cyclin positivity (10.2 .+-. 6.7% vs. 2.7 .+-. 2.5% [P < 0.0001]). S-phase fraction measured by FCM was 7.9% .+-. 5.7% for carcinomas and 3.17% .+-. 2.1% for benign controls (P < 0.003). Ki-67 and Cyclin staining, as well as SPF, were significantly increased in aneuploid compared to diploid tumors, and increased staining was associated with worsening nuclear grade. There were significant correlations between SPF and Ki-67 staining (r = 48, P < 0.0001) and SPF and Cyclin staining (r = 0.48, P < 0.0001). We conclude that FCM and IA provide comparable measurements of DNA content, although occasional discrepancies occur. Image analysis provides a valuable alternative method for assessing tumor cell proliferation and may offer certain advantages over FCM.

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