Moesin and CD44 expression in cutaneous melanocytic tumours

Abstract

The ERM (ezrin, radixin and moesin) family members, located just beneath the plasma membranes, are thought to be involved in the association of action filaments with the plasma membrane. One of the family members, moesin, is reported to bind to CD44. Splice variants of CD44 are thought to be associated with tumour progression or differentiation. Our aim was to investigate immunohistochemically the expression of moesin together with CD44 on paraffin tissue sections of a series of melanocytic tumours. The material included 12 ordinary melanocytic naevi, six Spitz naevi, eight dysplastic naevi, six blue naevi, seven malignant melanomas in situ, 15 primary malignant melanomas, five metastatic melanomas to the skin and five lymph node metastases. In the normal skin and the melanocytic tumours the expression of moesin was largely similar to that of CD44 standard. Strong moesin staining was observed in benign melanocytic lesions and melanomas in situ. However, the expression was decreased in advanced malignant melanomas. The moesin labelling in melanoma cells was downregulated with the depth of dermal invasion. The immunoreactivity was also diminished in the skin metastases and the lymph node metastases of melanoma. These results suggest that in melanocytic tumours, the alternation in the expression of moesin may be involved in the progression of malignancy.

Reduced Level of CD44 and Hyaluronan Associated with Unfavorable Prognosis in Clinical Stage I Cutaneous Melanoma

“…26 Considering that cutaneous melanomas evolve in basal epidermis, surrounded by keratinocytes with high levels of CD44 46,47 and an environment rich in 48,49 Both high 50 -52 and reduced [53][54][55] CD44 expression levels have been associated with cancer growth and adverse prognosis in various malignant tumors, supporting the concept that the growth regulation of cancer cells by CD44 is highly dependent on the cellular background. 53,56 Supporting our findings, CD44 expression diminished with increasing invasiveness of primary tumors 30,31,34 and in metastatic melanomas. 33 However, in the only prognostic study concerning CD44 expression in cutaneous melanoma, high CD44 level in primary malignant melanomas (n ϭ 92) associated with progressive disease and poor univariate survival.…”

“…[27][28][29][30][31][32][33][34][35] As far as we know, the current series consisting of patients with localized disease is decisively larger than any previous report on the CD44 level and prognosis of cutaneous melanoma. Further, we have included novel data on the level of HA, the main ligand of CD44.…”

“…8,[17][18][19][20][21] Previous experimental data suggest that CD44 and HA enhance growth and metastatic capacity of melanoma cells, 17,18,[21][22][23][24][25][26] but the clinical significance of this suggestion has not been confirmed in the relatively small and divergent clinical materials reported so far. [27][28][29][30][31][32][33][34][35] We demonstrate here that the reduced stainings of cell surface CD44 and tumor cell associated HA are associated with each other, and with progressive disease and poor prognosis in localized cutaneous melanoma. cutaneous melanoma patients with sufficient clinicopathological and long-term follow-up data.…”

Altered Expression of the ERM Proteins in Lung Adenocarcinoma

“…Although several authors have speculated that the ERM proteins may play a role in cancer (Tsukita et al, 1994), data concerning their expression in tumors are rather limited (Akisawa et al, 1999;Ichikawa et al, 1998). Interestingly, the neurofibromatosis 2 (NF2) tumor suppressor gene encodes a protein (merlin or schwannomin) structurally related to the ERM family of proteins (Rouleau et al, 1993;Trofatter et al, 1993).…”

“…The ERM proteins bind to actin filaments at their carboxy-terminal domain (Algrain et al, 1993;Henry et al, 1995;Turunen et al, 1994), and to several integral membrane proteins, such as CD43, CD44, and ICAM-1, -2, and -3, and so on, at their aminoterminal domains (Heiska et al, 1998;Mangeat et al, 1999;Yonemura et al, 1998). The ERM proteins are involved in a variety of cellular functions, such as cell adhesion, migration, and the organization of cell surface structures (Bretscher et al, 1997;Mangeat et al, 1999;Martin et al, 1995;Sato et al, 1991Sato et al, , 1992.Although several authors have speculated that the ERM proteins may play a role in cancer (Tsukita et al, 1994), data concerning their expression in tumors are rather limited (Akisawa et al, 1999;Ichikawa et al, 1998). Interestingly, the neurofibromatosis 2 (NF2) tumor suppressor gene encodes a protein (merlin or schwannomin) structurally related to the ERM family of proteins (Rouleau et al, 1993;Trofatter et al, 1993).…”