Cell kinetic study of the endometrium by nonisotopic in situ hybridization for histone H3 messenger RNA and immunohistochemistry for Ki‐67 and for estrogen and progesterone receptors

Abstract

We investigated the cell kinetics of the endometrium in hysterectomy specimens taken for leiomyoma from 22 women with regular ovulatory menstrual cycles. Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating activity using histone H3 messenger RNA in situ hybridization (H3 mRNA-ISH) and immunostaining for the Ki-67 antigen. The relationship of the proliferative activity of endometrial cells to the immunohistochemical expression of the estrogen receptor (ER) and the progesterone receptor (PR) was also examined. During the menstrual cycle, H3 mRNA expression was observed in both the epithelial cells and the stromal cells of the endometrium. In the functional layer, the labeling indices for H3 mRNA (H3 mRNA-LIs) in the epithelial cells peaked in the late proliferative phase, decreased sharply in the early secretory phase, and remained unchanged thereafter. On the other hand, H3 mRNA-LIs of stromal cells displayed two peaks: one in the midproliferative phase and the other in the late secretory phase, the former peak being the greater. In the basal layer, epithelial cells and stromal cells showed low H3 mRNA-LIs and no significant variation throughout the menstrual cycle. The H3 mRNA-LIs correlated well with the Ki-67-LIs and were lower than the corresponding Ki-67-LIs. The regression coefficient (H3 mRNA-LIs against the Ki-67-LIs) was 0.33 for epithelial cells and 0.49 for stromal cells, suggesting that the cell cycle time was longer for epithelial cells than for stromal cells. The proliferative activity of endometrial cells showed close relationships with the expressions of ER and PR in the endometrium. When used in combination with other proliferative markers in paraffin-embedded tissue sections, H3 mRNA-ISH could open broader perspectives on the cell kinetics of the endometrium. Anat Rec 266: 234 -240, 2002.

ER, PR and Ki‐67 expression status in granulomatous and chronic non‐specific endometritis

“…In a normal menstrual cycle maximum Ki-67 expression in the endometrial cells is seen in the follicular phase which decreases by half during the early luteal phase and virtually ceases during the mid-and late-luteal phase. 18,19 Besides the premenstrual endometrium, the ER, PR and Ki-67 status have also been described in the post menopausal, hyperplastic and neoplastic endometria. 20 However, their levels in inflammatory lesions of endometrium have not been studied so far.…”

Histone mRNA in situ hybridization and Ki 67 immunohistochemistry in pediatric adrenocortical tumors

“…In our series, we found that Ki 67 expression was significantly higher in carcinomas than adenomas, and a Ki 67 LI ≥14.55 was found to be an indicator of malignancy for pediatric adrenocortical neoplasms. The assessment of cells in the S phase of the cell cycle is an alternative method for evaluating proliferating cells [2,5,10]. In situ hybridization of histone H3 and/or H4 mRNA is an assay used to detect S-phase cells in archival paraffin-embedded material [15,16].…”

“…During the S phase of the cell cycle, the level of histone mRNA increases over 50-fold and rapidly disappears at the start of G 2 . The rapid degradation of the histone mRNA after the S phase provides an opportunity to distinguish the proliferating cells in S phase by in situ hybridization for histone mRNA [2,10,15]. Rauttiainen et al reported that nonisotopic histone mRNA in situ hybridization is a reproducible method for measuring the proliferative activity of tumor cells and an independent prognostic factor in astrocytomas [16].…”

Histochemical, ultrastructural, and three-dimensional observation of smooth muscle cells in human gastric mucosa

“…Since H3 mRNA-ISH did not label SMCs in the LP, they are very stable cells, H3 mRNA-ISH being the most reliable method for the detection of S-phase cells in ordinary paraffin sections (Hayama et al 2002;Maeyama et al 1997). There is no information available concerning what kind of factors might control the proliferation and structure of these SMCs.…”