Afify Alaa M, Craig Sarah, Paulino Augusto F G, Stern Robert
Department of Pathology, University of California, Davis Health System, Sacramento, CA 95817, USA.
Ann Diagn Pathol. 2005 Dec;9(6):312-8. doi: 10.1016/j.anndiagpath.2005.07.004.
The interaction between epithelial tumor cells and their surrounding stroma is important in tumor progression and metastasis. This is accomplished through a number of transmembrane receptors that interact with stromal extracellular matrix molecules. One of these receptors, CD44, binds to extracellular matrix component hyaluronic acid (HA). The purpose of this study was to evaluate the significance of HA, CD44s, and CD44v6 in benign, hyperplastic, atypical, and malignant endometrial epithelia. Archival paraffin-embedded cell blocks from proliferative endometrium (n = 11), secretory endometrium (n = 12), simple hyperplasia (n = 13), complex hyperplasia without atypia (n = 9), complex hyperplasia with atypia (n = 17), and adenocarcinoma (n = 21) were stained for HA, CD44s, and CD44v6. HA was detected throughout the normal menstrual cycle but was more intense during the secretory phase. Only during the secretory phase was CD44s expressed in the stromal cells in 11 cases (92%), whereas CD44v6 was detected in glandular epithelium in 9 (75%). CD44s was expressed in the glandular epithelium in 2 (15%) cases of simple hyperplasia, 4 (44%) of complex hyperplasia without atypia, 14 (82%) of complex hyperplasia with atypia, and in 16 (76%) of adenocarcinoma. CD44v6 was expressed in the glandular epithelium in 1 (11%) case of complex hyperplasia without atypia, 17 (100%) cases of complex hyperplasia with atypia, and in 18 (86%) cases of adenocarcinoma, but in none of the cases of simple hyperplasia. The endometrial stromal cells expressed CD44v6 in 1 (8%) case of simple hyperplasia, 6 (67%) of complex hyperplasia without atypia, 8 (47%) of complex hyperplasia with atypia, and in 3 (14%) of adenocarcinoma. We concluded that in the normal menstrual cycle, the timing of peak staining of HA and CD44s in the stroma and the up-regulation of CD44v6 in secretory glands are coincident with the period in which the endometrium is most receptive to embryo implantation. HA is more abundant in the stroma adjacent to the tumor, suggesting that interactions between tumor cells and stromal HA promote tumorigenesis. With progression from hyperplasia and with increasing atypia to adenocarcinoma, levels of stromal HA, glandular CD44v6, and glandular and stromal CD44s all increase. Thus, HA and CD44 are both involved in the development and progression of endometrial cancer.
上皮肿瘤细胞与其周围基质之间的相互作用在肿瘤进展和转移过程中至关重要。这一过程通过多种与基质细胞外基质分子相互作用的跨膜受体来实现。其中一种受体CD44可与细胞外基质成分透明质酸（HA）结合。本研究旨在评估HA、CD44s和CD44v6在良性、增生性、非典型性和恶性子宫内膜上皮中的意义。对来自增殖期子宫内膜（n = 11）、分泌期子宫内膜（n = 12）、单纯性增生（n = 13）、复杂性非典型增生（n = 9）、复杂性非典型增生伴非典型性（n = 17）和腺癌（n = 21）的存档石蜡包埋细胞块进行HA、CD44s和CD44v6染色。HA在整个正常月经周期中均可检测到，但在分泌期更为强烈。仅在分泌期，11例（92%）基质细胞中表达CD44s，而9例（75%）腺上皮中检测到CD44v6。2例（15%）单纯性增生、4例（44%）复杂性非典型增生、14例（82%）复杂性非典型增生伴非典型性及16例（76%）腺癌的腺上皮中表达CD44s。1例（11%）复杂性非典型增生、17例（100%）复杂性非典型增生伴非典型性及18例（86%）腺癌的腺上皮中表达CD44v6，但单纯性增生病例中均未表达。1例（8%）单纯性增生、6例（67%）复杂性非典型增生、8例（47%）复杂性非典型增生伴非典型性及3例（14%）腺癌的子宫内膜基质细胞中表达CD44v6。我们得出结论，在正常月经周期中，基质中HA和CD44s染色峰值出现的时间以及分泌期腺体中CD44v6的上调与子宫内膜对胚胎着床最易接受的时期一致。肿瘤邻近基质中HA更为丰富，提示肿瘤细胞与基质HA之间的相互作用促进肿瘤发生。随着从增生到非典型性增加再到腺癌的进展，基质HA、腺上皮CD44v6以及腺上皮和基质CD44s的水平均升高。因此，HA和CD44均参与子宫内膜癌的发生和发展。
