Rodrigues Neesha A, Dillon Deborah, Carter Darryl, Parisot Nicole, Haffty Bruce G
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Cancer. 2003 Mar 15;97(6):1393-403. doi: 10.1002/cncr.11204.
Patients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients.
The study population consisted of 20 patients age < 42 years and 34 patients age > 60 years who were treated at Yale University School of Medicine with breast-conserving therapy (BCT) and whose archival paraffin blocks were available and had sufficient tumor for staining. The original slides from each case were reviewed and the most representative specimen block from each case was processed for immunohistochemical staining. Pathologic characteristics evaluated for each case included histology, grade, and presence of necrosis. Paraffin-embedded sections were immunohistochemically evaluated for expression of HER-2/neu, estrogen receptor (ER), progesterone receptor (PR), bcl-2, cyclin D1, Ki-67, and p53.
Although there was no difference in pathologic features of the tumors between the two groups, HER-2/neu was found to be overexpressed in a greater percentage of the younger population (P = 0.06). There was no apparent difference in expression of the other markers. Of note, HER-2/neu expression was correlated with high nuclear grade (P = 0.004), necrosis (P = 0.06), and ER and PR negativity (P = 0.01 and P = 0.03, respectively) in the combined population.
The current study data suggested that HER-2/neu overexpression in younger patients may characterize a biologic difference in their tumor and may partially contribute to their higher risk of recurrence. Further studies are needed to assess whether this difference holds independent of grade and to evaluate the prognostic significance of HER-2/neu overexpression in DCIS.
与年龄较大时被诊断为导管原位癌(DCIS)的患者相比,年轻时被诊断为此病的患者似乎有着不同的自然病史和生物学特性,包括更高的局部复发率。本研究比较了一组年轻女性中发生的DCIS与一组老年女性中发生的DCIS的各种病理和分子特征,以确定这两组患者之间潜在的生物学差异。
研究人群包括20名年龄小于42岁和34名年龄大于60岁的患者,他们在耶鲁大学医学院接受了保乳治疗(BCT),且有存档的石蜡块,并有足够的肿瘤组织用于染色。对每个病例的原始切片进行复查,并对每个病例最具代表性的标本块进行免疫组织化学染色处理。对每个病例评估的病理特征包括组织学、分级和坏死情况。对石蜡包埋切片进行免疫组织化学评估,以检测HER-2/neu、雌激素受体(ER)、孕激素受体(PR)、bcl-2、细胞周期蛋白D1、Ki-67和p53的表达。
虽然两组肿瘤的病理特征没有差异,但发现HER-2/neu在较年轻人群中的过表达比例更高(P = 0.06)。其他标志物的表达没有明显差异。值得注意的是,在合并人群中,HER-2/neu表达与高核分级(P = 0.004)、坏死(P = 0.06)以及ER和PR阴性(分别为P = 0.01和P = 0.03)相关。
目前的研究数据表明,年轻患者中HER-2/neu的过表达可能是其肿瘤生物学差异的特征,可能部分导致其较高的复发风险。需要进一步研究来评估这种差异是否独立于分级存在,并评估HER-2/neu过表达在DCIS中的预后意义。