Immunohistochemical assessment of tumor proliferation and volume of embryonal carcinoma identify patients with clinical stage A nonseminomatous testicular germ cell tumor at low risk for occult metastasis.

Abstract

Thirty percent of patients with clinical Stage A nonseminomatous testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a previous retrospective study at Indiana University, the combination of tumor proliferation rates by flow cytometry and histopathologic evaluation defined risk groups for occult metastatic disease in these patients with clinical Stage A NSGCT: A new immunohistochemical proliferation marker (MIB-1) was therefore used to assess growth fraction in combination with histopathology in an effort to predict pathologic stage in patients with clinical Stage A NSGCT: Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node dissection at Indiana University were histopathologically evaluated. Formalin fixed, paraffin embedded tissue sections were immunohistochemically stained using a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67 (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method based on microwave oven heating of paraffin sections. MIB-1 immunohistochemical staining showed significant differences in mean values between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients with pathologic Stage B NSGCT (P = 0.0032). The negative predictive value for patients with pathologic Stage A disease was 87% using a cut-off of 80% or less MIB-1 positively stained cells. A combined approach, using the absolute volume of embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (< or = 80%) was able to define a group of 30% of all patients who were at extremely low risk for occult metastatic disease. MIB-1 immunostaining in combination with histopathology aided in defining a low risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk for metastasis. The risk factors need to be tested in a prospective clinical trial to determine if they are potentially useful in assigning therapy to individual patients.