E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients.

OBJECTIVES: The treatment of choice for invasive penile carcinoma is amputation and lymphadenectomy. The latter is associated with a high morbidity rate. Analysis of new prognostic factors such as E-cadherin, matrix metalloproteinase (MMP)-2, and MMP-9 may help to select candidates for lymphadenectomy.

METHODS: We assessed 125 patients with penile epidermoid carcinoma treated with amputation and bilateral lymphadenectomy. The following factors were analyzed: age, race, disease evolution time, venereal background, clinical and pathologic stage, tumor thickness, differentiation grade, venous and lymphatic embolization, koilocytosis, type of invasion, and E-cadherin, MMP-2, and MMP-9 immunoreactivity. The value of risk factors for lymph node metastases and specific survival was assessed.

RESULTS: The mean follow-up was 76.5 months. Clinical N stage (P = 0.001), tumor thickness (P = 0.027), lymphatic permeation (P < 0.001), venous embolization (P = 0.002), corpus cavernosum infiltration (P = 0.002), and low E-cadherin expression (P = 0.032) significantly correlated with the presence of metastases. Independent risk factors for metastases were lymphatic permeation (relative risk [RR] = 5.99; 95% confidence interval [CI] 2.1 to 16.9) and clinical N stage (RR = 5.5; 95% CI = 1.9 to 16.7). Lymph node metastases (RR = 57.9; 95% CI = 7.4 to 453.9), urethral infiltration (RR = 3.5; 95% CI = 1.3 to 9.2), and MMP-9 immunoreactivity (RR = 3.2; 95% CI = 1.2 to 8.3) were considered independent risk factors for disease recurrence.

CONCLUSIONS: On univariate analysis, low E-cadherin immunoreactivity was associated with a greater risk of lymph node metastases. High MMP-9 immunoreactivity was an independent risk factor for disease recurrence.