Proliferating Cell Nuclear Antigen Expression to Predict Occult Disease in Clinical Stage I Nonseminomatous Testicular Germ Cell Tumors

Abstract

We analyzed primary tumor tissue from 89 clinical stage I nonseminomatous germ cell testicular tumor patients for proliferating cell nuclear antigen expression and histological features to determine if these elements could distinguish pathological stage I (52 patients) from pathological stage II disease or patients who later had relapse (37). Using a monoclonal antibody (PC10††Dako Corp., Carpinteria, California.) developed for use in archival tissue, nuclear proliferating cell nuclear antigen expression was immunohistochemically measured for the overall tumor (total proliferating cell nuclear antigen) and for each neoplastic cell type present. In addition, the primary tumor was examined for the presence of vascular invasion and determination of the percentage of tumor composed of embryonal carcinoma. Univariate logistic regression analysis revealed higher total (p = 0.0001) and higher embryonal carcinoma proliferating cell nuclear antigen expression (p = 0.0437) to be statistically significant risk factors for occult disease, correctly predicting its presence 73% and 61.5% of the time, respectively. More importantly, the presence of vascular invasion and a higher percentage embryonal carcinoma were highly significant risk factors for occult disease and were truly predictive in 80.4% and 77.2% of the cases, respectively. Multivariate logistic regression analysis revealed a combination of vascular invasion and percentage embryonal carcinoma to be the best model to predict occult disease correctly (85.9%). The addition of total or embryonal carcinoma proliferating cell nuclear antigen expression did not improve the clinical use of the model containing vascular invasion and percentage embryonal carcinoma. Although proliferating cell nuclear antigen expression mirrors the biological behavior of clinical stage I nonseminomatous germ cell testicular tumor to some degree, assessment of vascular invasion and percentage embryonal carcinoma has greater clinical use.