Influence of cathepsin D expression on prognosis in non-small cell lung cancer

Youm, Hyung Roul; Myeong, Jae Il; Lim, Jong Chul; Kim, Han Kyun; Lee, Nam Hun; Lee, Dae Ho; Ko, Hyang Mee; Moon, Jong Yeoung; Kang, Heon Seok; Rheu, Heong Seon; Kim, Wan; Park, Chang Soo; Park, Kyung Ok

Abstract

BACKGROUND
Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. METHOD: Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma).
RESULTS
Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression n stromal cells was significantly associated with p-stage in non-small cell lung cancer (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T-factor, nodal involvement, differentiation. Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with progonosis showed that nodal involvement was the only independent prognostic factor in all patients.
CONCLUSION
Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.