Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas

Knowing the differential expression of CD44 isoforms in intestinal- and diffuse-type gastric carcinomas, we used antibodies against the standard form of CD44 (CD44s) and the domain encoded by exon v6 (CD44v6) in 103 patients with primary gastric adenocarcinomas to explore the role of CD44 isoforms in metastases of both types of gastric cancer. Carcinomas of the intestinal type were more frequently CD44s and CD44v6 positive than carcinomas of the diffuse type (p = 0.034 for CD44s and p = 0.022 for CD44v6). The reactivity to these two antibodies did not correlate with histopathological and clinical prognostic factors in intestinal-type carcinoma. In contrast, expression of CD44v6 was associated with infiltrative tumor growth (p = 0.021), depth of invasion (p = 0.012), lymph node involvement (p = 0.005) and a higher incidence of distant metastasis (p = 0.069) in cancers of the diffuse type. CD44s-expressing diffuse-type tumors had a higher incidence of distant metastasis at presentation (p = 0.001), but expression of CD44s was not correlated with other clinicopathologic indices. For all cases, there was a nonsignificant association between CD44s expression and poor survival. Unexpectedly, there was also no significant difference in survival regarding expression of CD44v6 for all cases or the diffuse-type subset. This study showed the role of CD44v6 in invasion and metastases of diffuse-type gastric carcinoma and demonstrated the necessity of subclassifying tumor types when studying the clinical significance of CD44 in human cancers.