Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast
Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast
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DOI：
10.1097/pai.0b013e318047df6d
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发表时间：
2008-03-01
影响因子：
1.6
通讯作者：
Paulino, Augusto F.
中科院分区：
文献类型：
--
作者：
Afify, Alaa;McNiel, Maaya A.;Paulino, Augusto F.
背景：上皮性肿瘤细胞上的跨膜受体与周围细胞外基质分子之间的相互作用在肿瘤的进展和转移中起重要作用。CD44受体和细胞外基质成分透明质酸(HA)的关系就是这种相互作用的最好例证。本研究旨在探讨CD44s、CD44v6和透明质酸在正常乳腺组织、乳腺增生性病变和恶性乳腺间质中的表达及其相关性。材料与方法：正常乳腺组织(n=10)、导管内不典型增生(n=13)、导管原位癌(n=24)、I期浸润性导管癌(n=28)、II期浸润性导管癌(n=31)及相应的阳性淋巴结均取自手术病理资料。结果：CD44s在正常乳腺组织和良性乳腺组织中均有表达。CD44s在乳腺上皮中的表达随着偏离正常组织学程度的增加而逐渐降低：83%在DCIS中，46%在I期导管癌中，26%在II期导管癌中。CD44v6在正常乳腺、导管内增生症、DCIS、I期浸润性导管癌、II期癌和淋巴结转移癌中的阳性率分别为0%、15%、100%、82%、94%和100%。HA仅在间质中表达，而在上皮细胞中不表达。HA在正常乳腺组织的小叶间质中有微弱的表达，局限于导管内增生附近的一条窄而微弱的带，定位于DCIS周围的一条宽阔而清晰的带。浸润性癌间质透明质酸染色更弥漫、强度更强，在淋巴结转移灶周围尤为明显。结论：乳腺癌组织中CD44s表达降低，CD44v6表达增强，间质透明质酸染色增强。这些发现提示CD44s、CD44v6和HA在乳腺癌的发生发展中起互补作用。
Background: The interaction between transmembrane receptors on epithelial tumor cells and the surrounding extracellular matrix molecules is important in tumor progression and metastasis. This interaction is best exemplified by the relationship of the receptor CD44 and the extracellular matrix component hyaluronan (HA). This study seeks to evaluate the expression and the correlation of CD44s, CD44v6, and HA in normal, hyperplastic, and malignant breast epithelium and stroma.Materials and Methods: Archival paraffin-embedded tissue from cases of normal breast tissue (n = 10), intraductal hyperplasia without atypia (n = 13), ductal carcinoma in situ (DCIS) (n = 24), stage I infiltrating ductal carcinoma (n = 28), stage II infiltrating ductal carcinoma (n = 31), and their corresponding positive lymph nodes were retrieved from the surgical pathology files. Tissue sections were evaluated for the expression of CD44s, CD44v6, and HA in the epithelial and stromal cells by immunohistochemistry.Results: Ductal epithelial cells and myoepithelial cells expressed CD44s in all cases of normal and benign breast tissue. The expression of CD44s in breast epithelium progressively decreased with increasing deviation from normal histology: 83% in DCIS, 46% in stage I ductal carcinoma and 26% in stage II ductal carcinoma. The reverse trend was observed for CD44v6 in ductal epithelium: 0% in normal breast, 15% in intraductal hyperplasia, 100% in DCIS, 82% in stage I infiltrating ductal carcinoma, 94% in stage II carcinoma, and 100% of metastatic carcinoma in the lymph nodes. HA was noted exclusively in the stroma but not in the epithelial cells. HA was faintly expressed in the intralobular stroma of normal breast tissue, confined to a narrow faint band adjacent to intraductal hyperplasia and localized to a broad well-defined band around DCIS. Stromal HA staining was more diffuse and intense in infiltrating carcinomas and was particularly pronounced surrounding the metastatic deposits in lymph nodes.Conclusions: This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.