Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis

Abstract

The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (> 80% positive cells) was significantly associated with the grade of tumour differentiation (p < 0.01), with lymph node metastasis (p < 0.01) and with BM degradation (p < 0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p < 0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.

Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients

“…In this study, we clearly confirmed our earlier results as we found 9.1-fold increased cath B protein concentration as well as 5.6-fold increased total cath B activity and 3.2-fold increase in the fraction of cath B activity, stable at pH 7.5 (Werle et al, 1997b) in tumour compared with normal lung tissue homogenates. Our data concerning enzyme expression revealed by IHC agree with previous investigations (Higashiyama et al, 1991(Higashiyama et al, , 1993Ozeki et al, 1993;Inoue et al, 1994;Sukoh et al, 1994aSukoh et al, , 1994b demonstrating that more elevated levels of cath B were found in primary tumours, which invaded into lymph nodes. Noteworthy, fraction of cath B activity stable at pH 7.5 (cath B A7.5 ) steadily increased in more malignant lung tumours (from pN1 to pN3).…”

“…Our findings agree with other univariate-and the multivariate survival analyses of cath B IHC analysis in tumour cells of adenocarcinoma (Sukoh et al, 1994a(Sukoh et al, , 1994b. Moreover, Ozeki et al (1993) further differentiated AC patients and demonstrated prognostic significance of cath B for lung AC of the Clara cell type only, but not for other subtypes of AC patients.…”

“…Previous studies on cath B in lung tumours, using either homogenates (Krepela et al, 1990;Sedo et al, 1991;Ebert et al, 1994;Ledakis et al, 1996;Werle et al, 1997aWerle et al, , 1997b or IHC analysis of cath B (Higashiyama et al, 1991(Higashiyama et al, , 1993Ozeki et al, 1993;Inoue et al, 1994;Sukoh et al, 1994aSukoh et al, , 1994b, showed significantly enhanced expression of the enzyme at activity and protein levels in patients suffering from NSCLC. In this study, we clearly confirmed our earlier results as we found 9.1-fold increased cath B protein concentration as well as 5.6-fold increased total cath B activity and 3.2-fold increase in the fraction of cath B activity, stable at pH 7.5 (Werle et al, 1997b) in tumour compared with normal lung tissue homogenates.…”

“…Higashiyama et al (1991Higashiyama et al ( , 1993 demonstrated increased expression of cath B in lung adenocarcinomas. Sukoh et al (1994aSukoh et al ( , 1994b performed retrospective immunohistochemical studies, which showed that patients with tumours, strongly positive for cath B, had a significantly shorter overall survival compared with patients, which were negative for cath B. The authors recommended cath B as an independent prognostic marker in non-smallcell lung cancer (NSCLC), similar as concluded also by Inoue et al (1994).…”

“…metastasis (reviewed by Berquin and Sloane, 1995;Elliot and Sloane, 1996;Lah and Kos, 1998;Yan et al, 1998). There are a number of evidences, supporting this hypothesis: the levels of cath B in tumours were elevated above the levels in adjacent normal tissue as demonstrated for example in lung carcinoma (Trefz et al, 1989;Krepela et al, 1990;Sukoh et al, 1994aSukoh et al, , 1994bEbert et al, 1994;Ledakis et al, 1996;Werle et al, 1997aWerle et al, , 1997b, breast carcinoma (Lah et al, 1992(Lah et al, , 1995a, colon carcinoma (Shuja et al, 1991), head and neck carcinoma (Budihna et al, 1996), oesophageal carcinoma (Hughes et al, 1998) and glioma (Rempel et al, 1994;Mikkelsen et al, 1995). Elevated levels of the enzyme were also found in sera of tumour patients (Leto et al, 1997;Kos et al, 1997Kos et al, , 1998.…”