Abstract
BackgroundInteractions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear.MethodsWe examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma.ResultsCancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01).ConclusionOur results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid.
Highlights
Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases
HA is abundantly secreted from stromal fibroblasts in response to humoral factors derived from tumor cells [1]
CD44 and intracellular hyaluronic acid binding protein (RHAMM/IHABP) (CD168) [2,3] are representative HA receptors, which have been identified as members of the microtubule-associated protein (MAP) family
Summary
Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HAmediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. HA is abundantly secreted from stromal fibroblasts in response to humoral factors derived from tumor cells [1] It is associated with breast cancer progression. CD44 and intracellular hyaluronic acid binding protein (RHAMM/IHABP) (CD168) [2,3] are representative HA receptors, which have been identified as members of the microtubule-associated protein (MAP) family. Another of the HA receptors, CD168, Lugli et al immunohistochemically investigated the CD168 positivity of tumor cells and identified a significant correlation with biological aggressiveness in colorectal cancer [12]. The significance of CD168 in the prognosis of gastric cancer is not fully understood
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