MICROVESSEL DENSITY AND DISTRIBUTION IN DUCTAL CARCINOMA IN-SITU OF THE BREAST
MICROVESSEL DENSITY AND DISTRIBUTION IN DUCTAL CARCINOMA IN-SITU OF THE BREAST
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DOI：
10.1093/jnci/86.8.614
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发表时间：
1994-04-20
期刊：
影响因子：
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通讯作者：
SCHNITT, SJ
中科院分区：
文献类型：
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作者：
GUIDI, AJ;FISCHER, L;SCHNITT, SJ
背景：先前的研究表明微血管密度是浸润性乳腺癌的一个重要预后因素。然而，与导管原位癌（DCIS）相关的微血管的范围和分布尚未得到很好的定义。目的：我们的目标是确定DCIS中间质微血管的密度和分布，并研究微血管密度、组织病理学特征、HER 2/neu癌基因表达和肿瘤增殖率之间的关系。方法：对61例经医院病理证实的DCIS患者中的55例进行分析。每例DCIS病例的乳腺活检标本均保存在石蜡块中。福尔马林固定，石蜡包埋组织的组织切片用苏木精-伊红染色，并对因子VIII相关抗原，HER 2/neu癌蛋白和Ki-S1抗体检测的增殖相关抗原进行免疫染色。每个病例的因子VIII染色切片由两名病理学家独立检查，每个观察者对总体肿瘤相关基质微血管密度进行半定量评分，评分范围为1+至3+。对DCIS相关基质微血管密度进行定量微血管计数。还评价了是否存在与受累间隙基底膜直接贴壁的微血管袖套。结果：发现不同数量的微血管以弥漫的方式存在于DCIS累及的周围空间。大多数病例（53%）的半定量微血管评分为2+; 22%的病例为1+，25%为3+。定量微血管计数范围为17 - 80条血管/100 x视野（0.45 mm（2）），平均值+/- SD为42.9 +/- 16.6。通过半定量评估，粉刺型病变与3+微血管密度的相关性显著高于非粉刺型病变（P = 0.004）。分别通过半定量和定量分析确定，显著微血管密度的存在与显著间质纤维组织增生（P = 0.05和P = 0.04）、HER 2/neu表达（P = 0.03和P = 0.0002）和高Ki-S1增殖指数（P = 0.05和P = 0.01）显著相关。在55例病例中，21例（38%）发现了受累间隙周围的血管袖套，与组织学特征、HER 2/neu表达或Ki-S1增殖指数无关。结论：乳腺DCIS的特征是两种类型的间质微血管。第一种模式是弥漫性增加的间质微血管周围涉及的空间。这种模式在伴有明显间质纤维组织增生的粉刺型病变中尤为突出。第二种模式是仅在少数病例中存在的受累间隙的微血管袖套，并且似乎与评估的组织学特征无关，包括DCIS亚型。
Background: Prior studies have suggested that microvessel density is an important prognostic factor in invasive breast cancer. However, the extent and distribution of microvessels in association with ductal carcinoma in situ (DCIS) have not been well defined. Purpose: Our goal was to determine the density and distribution of stromal microvessels in DCIS and to investigate the relationships among microvessel density, histopathologic features, HER2/neu oncogene expression, and tumor proliferation rate. Methods: Of 61 consecutive cases of DCIS identified from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens had been preserved in paraffin blocks for each DCIS case. Histologic sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the proliferative-associated antigen detected by the Ki-S1 antibody. Factor VIII-stained sections from each case were independently examined by two pathologists and overall tumor-associated stromal microvessel density was scored semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel counts of DCIS-associated stromal microvessel density were performed. The presence or absence of a cuff of microvessels in immediate apposition to the basement membrane of involved spaces was also evaluated. Results: A variable number of microvessels were found to be present in a diffuse pattern surrounding spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative microvessel counts ranged from 17 to 80 vessels per 100x field (0.45 mm(2)), with a mean +/- SD of 42.9 +/- 16.6. Comedo-type lesions were significantly (P = .004) more often associated with 3+ microvessel density than non-comedo-type lesions by semiquantitative assessment. As determined by both semiquantitative and quantitative analysis, respectively, the presence of prominent microvessel density was significantly associated with marked stromal desmoplasia (P = .05 and P = .04), HER2/neu expression (P = .03 and P = .0002), and high Ki-S1 proliferation index (P = .05 and P = .01). Vascular cuffing around involved spaces was identified in 21 of the 55 cases (38%) and was not significantly associated with histologic features, HER2/neu expression, or Ki-S1 proliferation index. Conclusions: DCIS of the breast is characterized by two patterns of stromal microvessels. The first pattern is a diffuse increase in stromal microvessels surrounding involved spaces. This pattern is particularly prominent in comedo-type lesions with marked stromal desmoplasia. The second pattern is microvessel cuffing of involved spaces that is present in only a minority of cases and appears unrelated to histologic features evaluated, including DCIS subtype.