gms | German Medical Science

Cathepsin B is a lysosomal cysteine protease, which is involved in the degradation of the extracellular matrix in tumor growth. It has been investigated in various carcinomas of the gastrointestinal tract, lung, breast, and others. Correlations with clinico-pathological variables and a worse prognosis associated with a strong expression of cathepsin B have been observed in some studies. However, in gastric cancer, previous results were contradictory. In the present immunohistochemical study, gastric adenocarcinomas from 115 patients were included. All patients were treated by gastrectomy with D2 lymphadenectomy. 49 patients were women (42.6 %) and 66 (57.4 %) were men. The mean age was 64.4 years (range: 33 – 85). All carcinomas were classified according to the UICC, WHO, Laurén, Goseki and Ming classification. Formalin-fixed and paraffin-embedded specimens were immunohistochemically stained according to a standard ABC peroxidase method. The extent of immunoreactivity was scored semiquantitatively (score: 0 – 3) followed by statistical analyses including chi square tests, Spearman rho method and uni- as well as multivariate survival analysis. In 16 specimens (13.9 %) less than 5 % of the tumor area was positive (score 0). A weak expression ( in up to 35 % of the tumor area) was observed in 45 cases (39.1 %), whereas 54 patients (47.0 %) exhibited a strong reactivity (scores 2 and 3). Increase of the pTNM stage correlated with a significantly stronger expression of catepsin B (p < 0.05). If the different tumor types according to the Laurén classification were analyzed separately, intestinal-type carcinomas exhibited a strong correlation between cathepsin B positivity and higher pT and pN stages. In addition, a strong cathepsin B expression was associated with a lower survival probability if all cases or the subgroup of intestinal-type cancers was analyzed. Multivariate survival analysis revealed cathepsin B immunoreactivity as an independent prognostic factor. In conclusion, expression of cathepsin B is increased in higher tumor stages according to the UICC classification. This effect was pronounced in the subgroup of intestinal-type cancers. Furthermore, strong cathepsin B expression represents a marker indicating a worse prognosis for gastric cancer patients.