Evaluation of immunohistochemical expression of stem cell markers (NANOG and CD133) in normal, hyperplastic, and malignant endometrium

Abstract

Cancer stem cells (CSC) are a potential cause for recurrence, metastasis, and resistance of tumors to different therapeutic modalities like hormonal radiotherapy and chemotherapy. We investigated two CSC markers (NANOG and CD 133) in normal, hyperplastic endometrium and endometrial carcinoma. A total of 93 formalin-fixed paraffin-embedded tissue blocks were used for immunohistochemical expression of NANOG and CD133 markers. NANOG expression was detected in 88.37% of endometrial carcinoma cases compared to 15% of the normal proliferative endometrium and 60% of hyperplasia cases. In endometrial carcinoma, high NANOG expression was significantly correlated with high grade, deep myometrial invasion, lymph node metastasis, and high stage with p-values (0.009, 0.005, 0.014, and 0.003, respectively). CD133 was positive in 76.74% of endometrial carcinoma cases, and it showed a significant correlation with deep myometrial invasion, positive lymph node, positive lymphovascular invasion, and high stage (p-values 0.003, 0.001, 0.003, and 0.013, respectively). Normal endometrium showed less expression of CD133 (only 5%) than hyperplasia and endometrial carcinoma with a statistically highly significant difference (p less than 0.0001). Hyperplastic cases with atypia expressed higher CD133 than those without atypia (6 out of 12 versus 3 out of 18). However, this difference was not statistically significant (p-value 0.111). The cancer stem cell markers NANOG and CD 133 are expressed in a high percentage in endometrial carcinoma compared to normal and hyperplasia and their expression is positively correlated with the aggressive behavior of the tumor. High expression of these two markers in apparently normal tissue around the tumor and in hyperplastic conditions with atypia suggests the possibility to use NANOG and CD133 expression as a diagnostic marker distinguishing dysplasia from reactive atypia. Therefore, inhibition of these markers can be a promising method to stop the progression of early cancers.

Keywords: CD 133; NANOG; cancer stem cell markers; endometrial carcinoma; endometrial hyperplasia; immunohistochemical; normal endometrium.

Figure 1.

Photomicrograph demonstrates the immunohistochemical staining of NANOG and CD 133 in endometrial tissue: A – NANOG expression in the nuclei of normal proliferative endometrium at (40X); B – photomicrograph showing high-grade nuclear NANOG expression in endometrial hyperplasia (10X); C – Photomicrograph of endometrial carcinoma showing strong nuclear NANOG expression at high power (40X); D – Photomicrograph of atypical endometrial hyperplasia with CD133 cytoplasmic and membranous expression at low power (10X); E – Endometrial carcinoma with low grade staining for CD133 at low power (10X); F – The same case in the previous picture (E) at high power (40X).