Influence of cathepsin D expression in lung adenocarcinoma on prognosis: possible importance of its expression in tumor cells and stromal cells, and its intracellular polarization in tumor cells.
BACKGROUND
Cathepsin D, an aspartic lysosomal proteinase, has been described to be closely associated with tumor progression and prognosis in some human malignancies. The purpose of this study was to determine clinicopathological and prognostic significance of cathepsin D expression in lung adenocarcinoma.


METHODS
Expression of cathepsin D in 152 lung adenocarcinoma patients was immunohistochemically studied using the antihuman cathepsin D antibody.


RESULTS
Eighty patients (53%) showed negative immunoreactivities in tumor cells. The cathepsin D-positive patients (72 patients, 47%) were divided into two subgroups; granular type expression (48 patients, 31%) with its polarized expression mainly in the luminal side of the cytoplasm of tumor cells and basal type expression (24 patients, 16%) with its polarized expression mainly in the basal or infranuclear side of the cytoplasm. Patients with basal type expression showed significantly more marked scar formation (P = 0.042), and especially among the patients with stage I disease, those with basal type tended to show poorer prognosis (P = 0.071) than the others. Cathepsin D was also expressed in stromal cells within the tumor tissues, and 86 patients (57%) with moderate to massively infiltrating cathepsin D-positive stromal cells showed a lower grade of differentiation (P = 0.005) and higher scar grade (P = 0.0003) than those with few cathepsin D-positive stromal cells. Cathepsin D status in stromal cells was significantly associated with prognosis (P = 0.014), and in a multivariate analysis, its expression status in stomal cells was marginally an independent prognostic factor only among the stage I patients.


CONCLUSIONS
In determining significance of cathepsin D expression in this disease, it is important to consider separately its expression cell type and its polarization pattern in tumor cells within the tumor tissue. How ever, only cathepsin D status in stromal cells within the tumor tissue is a marginal marker influencing prognosis among stage I patients.
Higashiyama
M
M
Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Doi
O
O
Kodama
K
K
Yokouchi
H
H
Kasugai
T
T
Ishiguro
S
S
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D002402:Cathepsin D / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D017154:Stromal Cells / Q000201:enzymology
D002402:Cathepsin D