Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

Abstract

Summary In this study, the immunohistochemical expression of a new inducible elastase inhibitor, SKALP (skin-derived antileucoproteinase)/elafin, in the tissue of squamous cell carcinoma and uninvolved oesophageal mucosa was studied using a polyclonal rabbit anti-serum against SKALP/elafin. The results were compared with the immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and the TUNEL assay in serial sections. In non-malignant oesophageal mucosa, the expression of SKALP/elafin was localized in the cells of the stratified zone overlying the PCNA-positive basal zone. In oesophageal cancer, the incidence of the expression was significantly related to the degree of the differentiation of the tumour. Characteristically, the expression was almost limited in tumour cell nests that had a clear squamous phenotype. In tumour cell nests, the expression of SKALP/elafin was localized in the cells overlying PCNA-expressing cells and no expression was found in the cells that expressed PCNA; DNA fragmentation was often observed in the same cell layers as those in which SKALP/elafin immunoreactivity was found. This enzyme inhibitor is speculated to be involved in the induction of the cell differentiation and apoptosis of human squamous cell carcinoma cells of the oesophagus.Keywords: SKALP/elafin; oesophageal cancer; immunohistochemistry Squamous cell carcinoma (SCC) is the major histological type of oesophageal cancer in Japan, being one of the most lethal neoplasms of the digestive organs. At present, only limited numbers of patients can be cured by conventional therapy, such as surgical resection, irradiation and chemotherapy, one reason being that oesophageal cancer has an extremely high potential for invasion into the surrounding organs and for metastasis. Several proteases produced by the cancer cell itself have been reported to be associated with cancer invasion and metastasis (Liotta et al, 1980(Liotta et al, , 1986Wooley, 1984;Nakajima et al, 1987;Reich et al, 1988;Basset et al, 1990). Also several kinds of specific inhibitors of such proteases have been shown to inhibit cancer invasion and metastasis (Baker et al, 1990;Cajot et al, 1990;Albini et al, 1991;Declerck et al, 1992;Kennedy, 1994;Kobayashi et al, 1994Kobayashi et al, , 1995. Hence, the protease inhibitors could be considered to possess the potential to be a useful tool for the development of a new therapeutic method against cancer.Recently, a new inducible elastase inhibitor, SKALP (skinderived antileucoproteinase) has been isolated from psoriatic skin (Schalkwijk et al, 1990. SKALP has been shown to be a heat-stable, cationic protein with an apparent molecular weight of 9-11 kDa. DNA of SKALP has been cloned and sequenced (Schalkwijk et al, 1991) and has proved to be identical to elafin, which is a similar epidermal protease inhibitor described by Wiedow et al (1990). The expression of SKALP/elafin has not been found in the cells of normal epidermis but is found in differentiating cells of psoriasis and wound healing (Schalkwijk et...

Differential Regulation of Elafin in Normal and Tumor-Derived Mammary Epithelial Cells Is Mediated by CCAAT/Enhancer Binding Protein β

“…The expression of elafin has been investigated in squamous cell carcinoma of the human oral tissues, esophagus, and lung, showing that increased elafin expression was observed in well-differentiated squamous cell carcinoma (45)(46)(47). However, most of the poorly differentiated tumor cells showed the decrease in elafin expression and high elastase activity (48).…”

Serine Proteinase Inhibitors in the Skin: Role in Homeostasis and Disease

“…It is barely synthesized in normal epidermis but upregulated upon injury, infection and inflammation [63][64][65]. The SKALP/elafin gene is further expressed in submandibular glands [66] and certain carcinomas [67][68][69]. The primary translation product of SKALP/elafin-specific mRNA exhibits a molecular weight of 12.3 kDa.…”

Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer

“…Elafin is expressed in well-differentiated squamous cell carcinoma of the skin and esophagus but is lost in poorly differentiated tumors [10-13]. Elafin was found in tumor cell nests, and DNA fragmentation was noted in these cell layers, suggesting that elafin was involved in induction of apoptosis [13].…”