Differential expression of CD44v6 in metastases of intestinal and diffuse types of gastric carcinoma.

Abstract

Aims-To assess whether standard and variant isoforms of CD44 (CD44s, CD44v5, and CD44v6) have a diVerential expression profile in early versus advanced gastric adenocarcinoma of the diffuse and intestinal types and their metastases. Methods-Immunohistochemical expression of CD44s, CD44v5, and CD44v6 was evaluated in 14 early gastric cancers (nine intestinal and five diVuse) and 37 advanced adenocarcinomas (21 intestinal and 16 diffuse) as well as in 18 cases of perigastric lymph node metastasis. Ten normal and five metaplastic gastric mucosa samples were also included in the study. Results-Although no significant association was found between the degree of invasion and the CD44 expression profile, CD44v6 positivity was detected more frequently in metastases of intestinal-type carcinomas (66%) than in metastases of diVuse-type neoplasms (11%) (p < 0.05). Weak CD44s, CD44v5, and CD44v6 expression was observed focally in both normal and metaplastic gastric mucosa samples. Conclusions-These data suggest that CD44v6 expression may be involved in the production of lymph node metastases in intestinal-type gastric carcinoma but not in the diVuse-type disease, the metastatic potential of which is most likely unrelated to the CD44 family of adhesion molecules. (J Clin Pathol 1998;51:134-137) Keywords: gastric adenocarcinoma; intestinal carcinoma; diVuse carcinoma; CD44; immunohistochemistry; invasion; metastasis The CD44 family of cell surface adhesion molecules is expressed in a variety of normal and neoplastic tissues.1 This protein family has been linked to a number of functions including lymphocyte homing and activation, 2 3 haemopoiesis, cell-cell, and cell-extracellular matrix interactions, and cell migration. 4 To be able to exert such diverse eVects, CD44 generates numerous isoforms through a mechanism of alternative splicing. Some of these CD44 isoforms also seem to play a role in the production of tumour metastases.5 Specifically, a nonmetastatic cell line of a rat pancreatic adenocarcinoma has been shown to acquire metastatic potential when transfected with CD44 variants containing exon v6 (CD44v6), an aVect that can be blocked by anti-v6 antibodies. [6][7][8] With regard to gastric adenocarcinoma, its intestinal and diVuse-types have been shown to express CD44 isoforms diVerentially. Thus, whereas intestinal-type adenocarcinomas express CD44 variant isoforms containing exons v5 and v6, diVuse-type tumours are associated predominantly with CD44 isoforms that include exon v5 (CD44v5).9 In addition, CD44 seems to influence the prognosis of gastric carcinoma, because CD44 overexpression is associated with the development of an invasive phenotype, 10 and high tumour recurrence and mortality rates in patients with curatively resected gastric cancer. 11In view of these relations between the biological behaviour of gastric carcinoma and its CD44 expression status, investigation into the possible diVerences between the CD44 expression profiles of early and advanced gastric cancers of intestinal and diVuse-ty...

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

“…However, the direct role of CD44v in the metastatic process has remained obscure. It has been reported that CD44v6 in gastric cancer was related to tumor growth and metastasis, especially in lymph node metastasis (13,14). In our study, we demonstrated a significant relationship between CD44v6 expression and lymph node metastasis, lymphatic invasion, depth of invasion and stage by univariate analyses.…”

“…It has been reported that CD44v6 is correlated with regulating tumor invasion, progression and metastasis in various kinds of malignancies including gastric cancer (11,12). In addition, CD44v6 was significantly correlated with lymph node metastasis in gastric cancer (13)(14)(15).…”

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

“…Another reason for such discrepancies is probably the comparison of results having different techniques [9] . T he cor relation between clinicopathological parameters and CD44 expression in the tumor is known to be different between intestinal and diffuse types of gastric carcinoma [29,30] . A study showed that the intestinaltype was more frequently CD44s-and CD44v6-positive than the diffuse-type tumor [15] , although the reactivity to these two antibodies did not correlate with histopathological and clinical prognostic factors in intestinal-type carcinoma [31] .…”

MicroRNA-34 dysregulation in gastric cancer and gastric cancer stem cell

“…It has been reported that CD44 isoforms containing variant exon 6 (CD44v6) is correlated with tumour invasion, progression and metastasis in various kinds of malignancies, including GC. [73][74][75] Lau et al 3 reported that CD44v8-10 is the major CD44 variant in GC and verified its role as a GCSC marker. The invasive and migratory capacities of the CD44(+) GC stem-like cells were much higher compared with those of the CD44(−) cells.…”