Investigation Of Receptivity Markers For Endometrial Cancer Treatment Development

Hyaluronan is an extracellular matrix protein that is involved in cell-cell and cell-matrix interactions. Hyaluronan performs this activity through hyaladherins, which are intracellular and extracellular receptors.

The purpose of this study was to compare the distributions of Hyaluronan Synthetase 2 (HAS2) and CD44s in healthy endometrial tissue samples obtained during the proliferative phase endometrium (PPE) and secretory phase endometrium (SPE), as well as pathologic samples diagnosed with benign endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), early stage of endometrial carcinoma (EC) (stage I/II) and advanced stage of endometrial carcinoma (stage III/IV) (n:5, each).

By using the avidin-biotin-peroxidase method, tissue samples that had been fixed with formalin passed through a regular paraffin follow-up protocol, and subsequently embedded in paraffin were stained indirectly with anti-CD44s and anti-HAS2 primary antibodies. Immunostaining intensity was graded as 0: negative, 1: weak, 2: moderate, 3: strong, and 4: very strong using a semiquantitative technique. The ANOVA test was used to assess the statistical significance of the findings. Statistical significance was defined as (p) values less than 0.05.

While weak HAS2 and weak/moderate CD44s immunoreactivity was observed on the surface epithelium (SE)/glandular epithelium (GE) and stroma of the tissue samples acquired during PPE; weak/moderate HAS2 and moderate CD44s immunoreactivity were observed in SPE and EH groups; moderate/strong HAS2, strong CD44s immunoreactivity was observed in EIN; strong/very strong HAS2 and very strong CD44s immunoreactivity were observed in early-stage EC and advanced stage EC. It was determined that the immunoreactivity intensity increased at a statistically significant level in both early and advanced stage EC.

The fact that HAS2 and CD44s, two intracellular receptors, have increased in endometrial carcinoma leads us to believe that they are likely to play a role in tumor development, invasion, migration, metastasis and that they may be useful in developing future treatment protocols targeting hyaluronan receptors.