Independent Prognostic Value of the 67-kd Laminin Receptor in Human Prostate Cancer

Extract

Widespread screening for early detection of prostate cancer has resulted in a dramatic rise in the proportion of clinically silent prostate malignant lesions (1–5). To date, no reliable predictors of the risk for such lesions to progress are available. Therefore, the urologist faces the therapeutic dilemma of whether to perform a radical treatment (prostatectomy or external radiotherapy) with the knowledge that some patients will have treatment complications with uncertain survival benefit or to carefully watch this group of patients with the known risk that some will experience the morbidity of clinically overt disease. Furthermore, for many patients, the extent of their prostate carcinoma is underevaluated and unpredictable, which results in inadequate therapeutic strategies (6–9).

Genes involved in the invasive and metastatic phenotype of cancer cells are potential candidates to serve as markers of tumor aggressiveness. The interaction between cancer cells and laminin, a major basement membrane glycoprotein (10), is considered to be a determining event in tumor progression (11–16). Among the several cell surface proteins that are able to interact with laminin (17), the 67-kd laminin receptor (67LR) (18,19) is involved in the chemotactic migration of malignant cells toward laminin (20,21). Compared with the normal tissue counterpart, 67LR expression is increased in a variety of human cancers, including breast (22–24), colon (25–27), gastric (28), ovarian (29), endometrial (30), lung (31,32), thyroid (33), and hepatocellular carcinoma (34); furthermore, this increase in 67LR is also associated with the biologic aggressiveness of the cancer cells (22–25,28,29). At the time we initiated this study, there were no data on the status of 67LR expression in prostate carcinoma. We, therefore, have examined 67LR expression in a large cohort of patients with prostate adenocarcinomas, including primary prostate tumors and prostate cancer lymph node metastases. Three groups of patients were included in the study. One group included 167 patients with localized prostate cancers (94 organ-confined tumors [pathologic stage T2] and 73 tumors with extracapsular extension [pathologic stage T3]) (35). Results from postoperative monitoring of total serum prostate-specific antigen (PSA) levels were available for 140 of these patients who had been followed for a mean length of time of 20 months (95% confidence interval [CI] = 16.89–22.73). The patients were followed every 3–4 months during the first year after surgical intervention, every 6 months for the next 2 years, and then annually with PSA measurements and digital rectal examinations. In our series, no patient with undetectable PSA levels had a documented tumor recurrence. In the second group comprising 24 patients, a transurethral resection of the prostate was performed because of urinary outlet obstruction due to massive prostatic urethra involvement by the prostate cancer. All of these patients had evidence of skeletal metastases on bone scanning or standard x ray. In the third group of patients, 24 prostate cancer pelvic lymph node metastases specimens were surgically obtained from staging ileoobturator lymph node dissections as a first step of a radical prostatectomy. There were no suspicious findings from preoperative chest x ray and bone scanning in all of these case subjects.