Tumor Proliferative Activity is Predictive of Pathological Stage in Clinical Stage a Nonseminomatous Testicular Germ Cell Tumors

Abstract

Purpose Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer. Materials and Methods Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis. Results After multiple logistic regression analysis, the G 2 M + S cell cycle fraction of the aneuploid tumor stemline was the most predictive parameter of pathological stage (p = 0.0004). Using a cutoff of 41 percent, patients with metastasis were predicted with a sensitivity of 71 percent. Of 61 patients with a G 2 M + S value of less than 41 percent, 53 had pathological stage A cancer (negative predictive value 87 percent). A low volume of embryonal carcinoma was predominant in patients at low risk for metastasis and MIB-1 immunohistochemical staining identified 23 percent of patients with pathological stage A tumor who were at extremely low risk for metastatic disease. Conclusions Assessment of tumor cell proliferation cannot classify accurately high risk patients at a clinically applicable level. However, identification of patients at low risk for metastasis by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma may be possible at the 90 percent level. MIB-1 staining is able to classify patients at extremely low risk for metastasis. These parameters deserve further study, since identification of patients at extremely low risk for metastasis could potentially decrease overall morbidity in the management of clinical stage A nonseminomatous testis cancer.