S‐phase fraction after gating on epithelial cells predicts recurrence in node‐negative breast cancer

Abstract

We have compared the prediction of distant recurrence for S-phase fraction (SPF) and DNA-ploidy, as estimated by flow cytometry, on an epithelial cell population and an unselected cell population from 268 node-negative breast-cancer patients diagnosed between 1985 and 1988. The tumor tissue was mechanically disintegrated and divided for flow cytometric analysis using both gated cells containing cytokeratin 8 and 18 and ungated cells treated with a detergent-trypsin solution. The relationship to distant recurrence was investigated for flow cytometric data, tumor size and estrogen and progesterone receptor content in univariate and multivariate Cox's regression analysis. The regression analyses were performed on 209 cases with S-phase fractions estimated by both methods. In 11 cases, DNA-ploidy classification differed, reflecting increased sensitivity to minor aneuploid peaks but a decreased ability to separate peaks in the near-diploid region for the gated populations. When SPF were used in univariate analysis as a continuous parameter or the upper tertile was used as cut-off value, SPF from the cytokeratin-gated cell population were most closely associated with recurrence and contributed additional prognostic information to SPF from the unselected cell population in the multivariate analysis. Out of the following variables:tumor size, ER and PR status, SPF and DNA ploidy, only SPF from immunoselected cells contributed prognostic information in multivariate analysis. These results indicate that SPF from immunoselected cell populations improves the prediction of recurrence in node-negative breast cancer.

Synthesis of 3,3‐Disubstituted Oxindoles by Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides: Reaction Development and Mechanistic Studies

“…We are aware of seven studies that focus on N0 disease. In five of these studies,14, 19, 23, 30, 36 including four after multivariate analysis14, 23, 30 with one involving only DNA diploid tumors,19 SPF was found to be correlated with outcome. In 2 other studies, involving 421 and 340 patients, respectively, no correlation between SPF and outcome was found 17, 24…”

“…Throughout the literature on FCM involving fresh or frozen material, despite the lack of a standardized method (like the one yielded by the ACC guidelines), there is agreement regarding the prognostic impact of DNA ploidy; 17 of 23 studies13–29 (including 813, 15–17, 19, 20, 22, 24 after multivariate analysis) revealed significant prognostic impact. There was even better agreement regarding the prognostic impact of SPF; 21 of 24 studies13–16, 19–23, 25–27, 30–38 (including 1714–16, 19–23, 25–27, 30, 31, 34, 35, 37, 38 after multivariate analysis) revealed significant prognostic impact. The same conclusions were drawn by Wenger et al,39 who also reviewed the relevant literature (series involving > 100 patients) on SPF and breast carcinoma in the last decade.…”

Proliferative activity in primary breast carcinomas is a salient prognostic factor

“…1 FCM is recognized as one prognostic factor among numerous others, but until the current study, it was considered to be less predictive than T status, tumor grade, hormone receptor status, and N status. Throughout the literature on FCM involving fresh or frozen material, despite the lack of a standardized method (like the one yielded by the ACC guidelines), there is agreement regarding the prognostic impact of DNA ploidy; 17 of 23 studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (including 8 13,[15][16][17]19,20,22,24 after multivariate analysis) revealed significant prognostic impact. There was even better agreement regarding the prognostic impact of SPF; 21 of 24 studies 13-16,19 -23,25-27,30 -38 (including 17 14 -16, 19 -23,25-27,30,31,34,35,37,38 after multivariate analysis) revealed significant prognostic impact.…”

Flow Cytometric DNA Analysis with Cytokeratin Gating of Formalin-Fixed Deparaffinized Breast Cancer Nuclei

“…5 The advantages of CK-gating for FT also should apply to PT breast cancers, particularly when accurate S-phase fraction calculation is the analytic goal. Our retrospective series identified 4 advantages of CK gating in the performance of flow DNA analysis of deparaffinized breast cancers: (1) from the paraffin blocks, and nuclear cytocentrifuge slides were studied to exclude normal ductal epithelium as the source of the DNA diploid CK-positive events.…”

“…5 20 Exclusion of nonepithelial cells from CK-gated flow DNA histograms increases the accuracy of S-phase fraction calculati on i.5,io-i4,i7,19,20 anc j e n n a n c e s the prognostic value of DNA flow cytometry.…”