Immunohistochemistry Panels to Help Understand Differentiation and Maturation of Mesonephros and Meanephros

Document Type

Conference Proceeding

Publication Date

3-2020

Publication Title

Laboratory Investigation

Abstract

Background: Mesonephros (MS) acts as embryonic renal tissue transiently. It forms metanephric duct and finally differentiates into mature kidneys. MS is also a source of somatic cells in the male gonad, versus ovarian tissue which has paramesonephric origin. Histology of MS and metanephros (MT) is partially established. However, demonstration of differentiation and maturation of these embryonal structures has not been studied extensively, especially using immunohistochemical (IHC) staining methods. Therefore, IHC staining was employed in this study to compare the expression patterns of MS and MT in an attempt to better understand its differentiation and maturation. Design: 4 MS (6 to 10 weeks) and 10 MT (10 to 36 weeks) were included in the study and paraffin embedded tissue with MS and/ or MT was sectioned and stained with two panels of antibodies; panel targeting stem cell/ progenitor cell population, including PAX8, OCT3/4 and CD133 and panel targeting growth factors and maturation/ mesenchymal markers, including mTOR, downstream signal p70S6K, WT-1 and vimentin. Light microscopy for each stain was evaluated and scored from negative (0) to positive (1+ to 3+; weak/fine to strong/granular staining). Results: PAX8 was expressed in glomeruli and renal tubules at all stages of MT development. OCT3/4 was absent in all renal tissues. However, OCT3/4 was expressed in the gonadal portion of a 10 week transforming MS (phenotypically male) with negative for PAX8 staining (Figure 1). CD133 was negative in MS and MT glomeruli. MS and early MT showed extensive expression of mTOR, p70S6K, WT1 and vimentin in glomeruli and interstitium. Whereas, from 17 to 36 weeks of gestation, there was a graduated weakening of staining of these markers in the interstitium of MT, which was replaced by expanding renal tubules (negative for WT-1 and vimentin). With maturation, the glomeruli showed fading of mTOR and p70S6K staining and retained WT-1 and vimentin immunoreactivity, even in late stages of MS development (fetal kidneys). Conclusions: OCT3/4 was expressed in gonadal tissue (most likely male fetus) that lacked PAX8 staining. This might help explain why testicular neoplasms show OCT3/4 staining whereas PAX8 is usually positive in renal and ovarian epithelial tumors. Mesenchymal to epithelial transformation in MT is characterized by graduated silencing of growth factors and disappearance of WT-1 and vimentin in the interstitial tissue of kidney.

Volume

100

Issue

Suppl 1

First Page

1735

Comments

United States and Canadian Academy of Pathology (USCAP) 109th Annual Meeting, February 29 - March 5, 2020, Los Angeles, CA

Last Page

1735

DOI

10.1038/s41374-020-0398-3

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