Oncotarget

Research Papers: Pathology:

Immunohistochemical analysis of RHAMM expression in normal and neoplastic human tissues: a cell cycle protein with distinctive expression in mitotic cells and testicular germ cells

Yao-Tseng Chen, Zhengming Chen and Yi-Chieh Nancy Du _

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Oncotarget. 2018; 9:20941-20952. https://doi.org/10.18632/oncotarget.24939

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Abstract

Yao-Tseng Chen1, Zhengming Chen2 and Yi-Chieh Nancy Du1

1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, 10065 NY, USA

2Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, 10065 NY, USA

Correspondence to:

Yi-Chieh Nancy Du, email: nad2012@med.cornell.edu

Keywords: RHAMM; human tissues; normal; neoplastic; testicular; Pathology

Received: November 15, 2017     Accepted: March 06, 2018     Published: April 20, 2018

ABSTRACT

Expression of Receptor for Hyaluronic Acid Mediated Motility (RHAMM) increases cellular motility and RHAMM overexpression promotes invasive phenotype and metastasis of cancer cells. RHAMM has been suggested as a biomarker for poor prognosis in several tumor types, including lung, breast, colorectal, gastric, pancreatic ductal, and ovarian cancers. RNA studies showed restricted RHAMM expression in normal tissues, but its protein expression data in tissues were limited. In light of its potential as a prognostic marker and a therapeutic target, we performed immunohistochemical analysis to systematically characterize RHAMM expression in normal and neoplastic human tissues. Among 29 normal adult tissues, RHAMM protein showed restricted expression and was observed in the thymus, lymph node/tonsil, small intestine, colon, skin, bone marrow, placenta, and testis. The cellular distribution patterns of RHAMM in these normal tissues were consistent with RHAMM being a G2/M cell cycle protein, and this was further supported in comparison to the expression of cyclin B2, another G2/M protein. However, unlike the subcellular localization of cyclin B2, RHAMM decorated mitotic spindles in both anaphase and metaphase. RHAMM expression in tumor tissues is variable; and higher RHAMM protein expression is associated with histologically higher-grade tumors in general. Distinct from its expression in somatic tissues, RHAMM showed diffuse, strong, stage-specific expression in the spermatocyte stage of germ cells in adult testis. The neoplastic counterpart, spermatocytic tumor, also showed strong RHAMM expression. This unique expression in testis suggests that RHAMM may function during normal testicular germ cell maturation.


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