CD44, a major surface receptor for hyaluronic acid, has multiple isoforms and represents a major cancer stem cell marker for various epithelial tumors. CD44 variant 9 (CD44v9) was correlated with recurrence and metastasis in gastric and colon cancer. We examined its role in invasion and as a biomarker for the basal muscle invasive molecular subtype showing worse prognosis, and for tumor progression in high risk (pT1/high grade) non‑muscle invasive bladder cancers (NMIBCs). CD44v9, cytokeratin 5/6 (CK5/6), and cytokeratin 20 (CK20) expression was evaluated by immunohistochemistry in 98 pathologically confirmed specimens (36 muscle and 62 high‑risk non‑muscle) and correlated to clinical outcome. In vitro analysis was performed using two human bladder cancer cell lines (HT1376 and 5637). The CD44v9 high‑expressing group exhibited significantly lower progression‑free and cancer‑specific survival rates in both muscle (P=0.0349 and 0.0382, respectively) and non‑muscle (P=0.0002 and 0.0079) invasive patients. CD44v9 expression was significantly correlated with CK5/6 (P<0.001), colocalizing at the muscle invasion front but distinctly separated from CK20 in non‑muscle invasion. CD44 and CD44v9 siRNA knockdown demonstrated significantly lower Matrigel invasion ability and significantly shorter migration distance (all P<0.01). CD44 and CD44v9 knockdown increased E‑cadherin and decreased N‑cadherin, snail, and slug epithelial‑mesenchymal transition marker protein expression. Thus, higher CD44v9 expression was associated with worse prognosis, likely impacting invasion and migration via the epithelial‑mesenchymal transition. Together, these findings suggest that CD44v9 expression might be a useful predictive biomarker in basal‑type muscle and high-risk NMIBC.

Background-Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori. Aim-To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. Methods-Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; nonulcer dyspepsia, n = 20) and from H pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. Results-Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. Conclusions-Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma. (Gut 1999;45:20-23)

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(J Clin Pathol 1998;51:396-398)