Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis

Abstract

Purpose: Interactions of hyaluronic acid (HA) with its binding protein RHAMM (receptor for HAmediated motility) have been proposed as being important in promoting tumour progression and dissemination. This comparative study was designed to investigate the RHAMM expression patterns in endometrial carcinoma. Methods: We examined a series of 89 endometrial carcinomas and 15 normal endometrial tissues by immunohistochemistry, using a RHAMM-specific polyclonal antibody. Expression of RHAMM was assessed according to the pattern and intensity within (overall cytoplasm, center/periphery of tumours) and between the tumours. The staining results were compared to the corresponding clinical data (age, menopause status, histological staining, histological grading, lymph node status). Results: RHAMM-expression was detectable in 58% of the 89 tumours [Histological stage: pT1a (8/12); pT1b (16/37); pT1c (18/26); pT2 (6/9); pT3a (4/5)] and 13% (2/15) of the normal endometrial tissues. The positivity rates for RHAMM were 100% in patients with positive lymph nodes but only 50.7% in patients with negative lymph nodes (P<0-01). Additionally, the expression pattern showed a highly significant correlation (P<0.01) with the histological grade of the tumours [G1 (6/42), G2 (33/34), G3 (13/13)] and occurrence of lymph node metastases. Conclusions: Our results suggest that RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas.

Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation

“…RHAMM is also crucial for transformation, metastasis, invasion, growth, and modification of the RAS signaling cascade [12–16]. Multiple forms of RHAMM are overexpressed in a broad variety of solid tumors such as endometrial carcinoma [17], breast cancer [18], pancreatic cancer [19], stomach cancer [20], squamous cell lung carcinoma [21], and malignant melanoma [22], as well as in hematological malignancies like AML, MDS, B-CLL, and multiple myeloma [23, 24]. Seventy percent of AML patients overexpressed RHAMM at both mRNA and protein level [24, 25].…”

Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma

“…In human tissues, low mRNA expression of RHAMM is found in lung and pancreatic tissue, and high mRNA expression of RHAMM is only detectable in testis, thymus, and placenta [6]. In contrast, RHAMM is upregulated in a number of cancers including pancreatic [7, 8], stomach [9], endometrial [10], bladder [11], colon [12], prostate [13, 14], breast [7, 15], head and neck [16], and glioblastoma [17]. RHAMM has been shown to have both extracellular and intracellular functions [18].…”

Production of Hyaluronan by the Trophectoderm is a Prerequisite for Mouse Blastocyst Attachment

“…Furthermore, hyaluronan-CD44 interaction, was demonstrated to be employed by the embryo and uterine cells in vitro 27 . These conflicting phenotypes may imply the redundant character of hyaluronan metabolism and receptor binding as previously demonstrated 12,28 .…”