Pujol P, Daurès J P, Brouillet J P, Maudelonde T, Rochefort H, Grenier J
Service de Biologie Cellulaire, Centre Hospitalier Universitaire de Montpellier-Nîmes, France.
Br J Cancer. 1999 Feb;79(5-6):909-14. doi: 10.1038/sj.bjc.6690145.
Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg(-1) and 11 ng mg(-1) respectively, P = 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg(-1) and 14 ng mg(-1) respectively, P = 0.0001). No differences in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status.
许多研究探讨了pS2作为激素反应性标志物以及组织蛋白酶D（组织蛋白酶D）作为乳腺癌预后因素的临床价值。由于pS2和组织蛋白酶D在人乳腺癌细胞系中均由雌激素诱导产生，我们研究了手术时月经周期阶段和绝经状态对乳腺癌中这些蛋白质水平的影响。对1750例乳腺癌患者进行了分析，其中包括339例处于月经周期的女性。通过放射免疫分析法测定肿瘤组织中的组织蛋白酶D和pS2。手术当天的血清雌二醇（E2）、孕酮（Pg）、促卵泡激素（FSH）和促黄体生成素（LH）水平用于确定绝经前女性的激素阶段。与黄体期相比，卵泡期的平均pS2水平有升高趋势（分别为17 ng mg⁻¹和11 ng mg⁻¹，P = 0.09）。绝经患者的平均pS2水平低于处于月经周期的女性（分别为8 ng mg⁻¹和14 ng mg⁻¹，P = 0.0001）。在月经周期的不同阶段之间，以及绝经前和绝经后女性之间，未观察到组织蛋白酶D平均水平的差异。在总体人群中，pS2与E2和Pg水平呈轻度正相关，与FSH和LH呈负相关，这可能反映了pS2与绝经状态之间的联系。在绝经前女性中，未发现pS2与E2、Pg、FSH或LH水平之间存在关联。在总体人群中，组织蛋白酶D水平与循环激素水平之间无相关性。然而，在绝经前患有雌激素受体阳性（ER +）肿瘤的女性亚组中，E2与pS2和组织蛋白酶D均有轻度关联，这与雌激素在ER +乳腺癌细胞系中诱导这些蛋白质产生一致。在整个月经周期和绝经过程中，乳腺癌中的pS2水平会发生变化。这表明选择pS2临界值时应考虑手术时的激素状态。相比之下，组织蛋白酶D水平与月经周期和绝经状态无关。
