Summary We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P<0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer Dowle et al., 1987;Kallioniemi et al., 1987a) and the content of oestrogen and progesterone receptors (Bichel et al., 1982;Moran et al., 1984;Coulson et al., 1984;Horsfall et al., 1986;Kallioniemi et al., 1987a). Whether DNA ploidy is an independent prognostic indicator or merely related to other prognostic factors is unclear (McGuire & Dressler, 1985;Cornelisse et al., 1987;Dowle et al., 1987).In the present study we evaluated the clinicopathological correlations and prognostic value of DNA DNA flow cytometry Paraffin-embedded tumours were processed for DNA flow cytometry by a previously described modification (Kallioniemi et al., 1987a) of the method of Hedley and coworkers . Briefly, 50 jgm sections from the paraffin-embedded tumours were dewaxed with xylene, rehydrated and digested overnight with trypsin. One to 6 sections from different parts of the primary tumour were processed for DNA flow cytometry. The nuclear suspension was stained with ethidium bromide, digested with RNAase and analysed with an EPICS C flow cytometer using 488 nm excitation. DNA index of aneuploid peaks and the coefficient of variation (CV) of all DNA peaks were Correspondence: O.-P. Kallioniemi.

To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as Sphase and G2/M-phase cell cycle fractions. Of these, DNA index and Sphase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a threefold risk of death as compared to DNA diploidy (P < 0.0001). The highest risk of death was associated with hypertetraploid (>2.20) DNA index, whereas a tetraploid DNA index (1.80-2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (<7%) SPF (type I DNA histogram) was associated with very favorable prognosis, whereas DNA aneuploidy with high DNA index (>2.20) or high (>12%) SPF (type 111 DNA histogram) was related to the worst prognosis with approximately eight-fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status. Cancer 62:2183-2190.1988. TATIC DNA CYTOMETRY has proved to be very valu-S able in the prediction of prognosis in breast cancer if both the modal DNA value and the scatter of DNA values in tumor cells are evaluated.' Auer and cow o r k e r ~ ~ ~ ~ have developed a cytophotometric classification of DNA histograms, which has considerable independent prognostic value in breast cancer. In flow cytometry DNA histograms are acquired from thousands of cells and thus have high statistical reliability. However, most investigators have recorded from the flow cytometric DNA his-tograms only one parameter, the DNA ploidy, which ap-From the

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The purpose of this study is to evaluate the risk factors of benign breast disease and to compare them with the known risk factors of breast cancer in order to make inferences on the relationship between benign breast disease and breast cancer. All benign breast lesions diagnosed from the population of the city of Tampere, Finland in 1974-1977 were reclassified by two pathologists into two groups of dysplasias and two groups of tumors. In the risk analysis of 422 age-matched pairs no group of benign lesions had risk factors consistently similar to those of breast cancer. It is therefore likely that either benign breast disease is not associate with breast cancer or it is an independent risk factor, not associated with the other high risk indicators of breast cancer.

The role of surgery in the treatment of acute hemorrhagic or necrotizing pancreatitis is discussed on the basis of a series of 996 patients with all types of acute pancreatitis who were treated in the years 1967--1976. Pancreatic resection was performed in 29 patients with hemorrhagic or necrotizing pancreatitis during the past 3 years. The extent of resection ranged from 60 to 100% of the pancreas. Eight patients died, for a mortality rate of 28%. Eight of 21 surviving patients developed diabetes requiring substitution therapy. During a follow-up period of 6 to 36 months, 17 patients were able to resume work, 3 are still convalescing, and 1 has retired.