Coulson P B, Thornthwaite J T, Woolley T W, Sugarbaker E V, Seckinger D
Cancer Res. 1984 Sep;44(9):4187-96.
Primary tumors from breast cancer patients were evaluated for the biochemical presence of three steroid cytosolic receptors and by DNA histogram analysis using flow cytometry. These parameters were compared with the histological and staging diagnoses and the patients' survival over a 36-month period. A total of 74 patients with primary breast tumors were evaluated. The breast samples invariably demonstrated a peak population of diploid G0/1 cells which contained 2C amounts of DNA, as determined by mixing experiments using normal human breast tissues or trout erythrocytes as fixed standards. The tumors were classified into five DNA histogram types based on their DNA index distributions established by flow cytometry. These results showed that 21% of the tumors were diploid and indistinguishable from the diploid population of normal breast cells, 8% were hypodiploid, 11% were hypertetraploid, 8% were multiploid, and the remaining 52% were hyperdiploid. The DNA index values varied from 0.78 (hypodiploid) to 2.60 (hypertetraploid). The percentages of S-phase cells were lowest in the diploid and hypertetraploid tumors and highest in the hypodiploid tumors. Among the 24 patients who died during the 36-month follow-up, 92% (22 of 24) were classified in one of the aneuploid groups. Three high-risk groups identified on the basis of survival after 36 months were distinguished: hypodiploid (50% survival); multiploid (43% survival); and hyperdiploid (50% survival). Rates of survival in the diploid and hyperdiploid groups were 87 and 71%, respectively. The hypodiploid group was distinguished by having the lowest mean estrogen cytosolic receptor value [26 +/- 13 (S.D.) fmol/mg], progesterone cytosolic receptor value (13 +/- 15 fmol/ mg), and androgen cytosolic receptor value (less than 1 +/- 1 fmol/mg). In contrast, the diploid tumors had some of the highest receptor values, with mean estrogen cytosolic receptor value equal to 102 +/- 114 fmol/mg, progesterone cytosolic receptor value equal to 74 +/- 110 fmol/mg, and androgen cytosolic receptor value equal to 65 +/- 80 fmol/mg. The lowest survival rates (17% after 36 months) occurred in patients over 67 years of age who had aneuploid tumors, compared to 100% survival in patients over 67 years of age with diploid tumors. Our results demonstrate the value of using flow cytometry and steroid receptor values as supplements to histopathology for the characterization of subgroups of mammary cancer patients. The ability to identify patients with a good prognosis compared to those at high risk of recurrence and death will be valuable in the design of future prospective treatment studies.
对乳腺癌患者的原发性肿瘤进行评估，检测三种甾体胞质受体的生化存在情况，并使用流式细胞术进行DNA直方图分析。将这些参数与组织学和分期诊断以及患者36个月的生存期进行比较。共评估了74例原发性乳腺肿瘤患者。通过使用正常人乳腺组织或鳟鱼红细胞作为固定标准的混合实验确定，乳腺样本始终显示出一个包含2C量DNA的二倍体G0/1细胞的峰值群体。根据流式细胞术确定的DNA指数分布，将肿瘤分为五种DNA直方图类型。结果显示，21%的肿瘤为二倍体，与正常乳腺细胞的二倍体群体无差异，8%为亚二倍体，11%为超四倍体，8%为多倍体，其余52%为超二倍体。DNA指数值从0.78（亚二倍体）到2.60（超四倍体）不等。S期细胞百分比在二倍体和超四倍体肿瘤中最低，在亚二倍体肿瘤中最高。在36个月随访期间死亡的24例患者中，92%（24例中的22例）被归类为非整倍体组之一。根据36个月后的生存期确定了三个高危组：亚二倍体（50%生存期）；多倍体（43%生存期）；超二倍体（50%生存期）。二倍体和超二倍体组的生存率分别为87%和71%。亚二倍体组的特点是雌激素胞质受体平均水平最低[26±13（标准差）fmol/mg]、孕酮胞质受体水平（13±15 fmol/mg）和雄激素胞质受体水平（小于1±1 fmol/mg）。相比之下，二倍体肿瘤的一些受体水平最高，雌激素胞质受体平均水平等于102±114 fmol/mg、孕酮胞质受体水平等于74±110 fmol/mg、雄激素胞质受体水平等于65±80 fmol/mg。67岁以上患有非整倍体肿瘤的患者生存率最低（36个月后为17%），而67岁以上患有二倍体肿瘤的患者生存率为100%。我们的结果表明，使用流式细胞术和甾体受体水平作为组织病理学的补充手段来表征乳腺癌患者亚组具有重要价值。与高复发和死亡风险患者相比，识别预后良好患者的能力在未来前瞻性治疗研究设计中将具有重要意义。
