No abstract

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.

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...