Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck

Abstract

CD9 is a transmembrane protein that has been implicated in cell adhesion, motility and proliferation, and numerous studies have demonstrated the prognostic value of its expression in different solid tumours. The purpose of this study is to determine the predictive value of CD9 in squamous cell carcinoma (SCC) of the head and neck. A total of 153 cases were examined for CD9 expression using immunohistochemistry applied on formalin-fixed, paraffin-embedded tissue. Cases were stratified in two categories depending on CD9 expression, as positive (X50% positive cells) or reduced (o50%). In all, 108 cases were positive for CD9 (85 cases with membranous, and 23 with both membranous and cytoplasmic staining) and 45 reduced expression. Reduced CD9 expression was significantly associated with high grade (P ¼ 0.0007) and lower disease-free survival (DFS) (P ¼ 0.017). The latter retained its significance in the multivariate analysis. When the 23 cases with both membranous and cytoplasmic patterns were studied as a separate subgroup, there were significant associations between CD9 expression and tumour grade (P ¼ 0.025) (95% CI 11 -68), tumour stage (P ¼ 0.08) (95% CI 3.5 -86) and the occurrence of any failure (P ¼ 0.083) (95% CI À1.7 -57). Immunohistochemical CD9 expression proved to be an independent prognostic factor in SCC of the head and neck, and it may detect patients at a high risk of recurrence. In addition, the cytoplasmic pattern seems to have an even more significant value. However, this finding is limited to the small number of cases with this pattern.

Contrasting Effects of EWI Proteins, Integrins, and Protein Palmitoylation on Cell Surface CD9 Organization

“…The latter result could help to explain CD9 tumor suppressor properties. Indeed, CD9 expression is often markedly reduced in malignant melanoma (13), colon (14), bladder (15), lung (16), pancreatic (17), squamous cell (18,19), and breast cancers (20,21). Furthermore, CD9 signaling can decrease cell proliferation while promoting apoptosis (22), and ectopic CD9 can suppress tumor cell motility and metastasis (23, 24), and down-regulate Wnt signaling pathways (25).…”

Tetraspanins and tumor progression

“…Reduced expression of CD9 is commonly observed in metastatic lesions compared with primary tumor, and patients with tumors lacking CD9 are typically at advanced stages. Although the prognostic importance of CD9 in the survival of tumor patients has not always been conclusive, most studies support the idea that CD9 expression in tumors correlates with better overall and/or disease-free survival rates, longer disease-free interval, and/or low recurrence rate [25, 49, 52, 55, 57, [62][63][64][65][66]. In contrast, two studies on gastric cancer suggest that higher CD9 expression appears to be associated with more progressive tumors and poorer prognosis [67,68].…”

Role of CD9 in proliferation and proangiogenic action of human adipose-derived mesenchymal stem cells

“…CD9 expression is often markedly reduced in malignant melanoma [21], colon [22], bladder [23], lung [24], pancreatic [25], squamous cell [26,27], and breast cancers [11,28]. Furthermore, CD9 signaling can decrease cell proliferation by promoting apoptosis [29].…”