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

Background. Thirty percent of patients with clinical Stage A nonsemino matous testicular germ cell tumor (NSGCT) are incorrectly clinically s taged. In a previous retrospective study at Indiana University, the co mbination of tumor proliferation rates by flow cytometry and histopath ologic 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 frac tion in combination with histopathology in an effort to predict pathol ogic stage in patients with clinical Stage A NSGCT. Methods. Primary o rchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lym ph node dissection at Indiana University were histopathologically eval uated. Formalin fixed, paraffin embedded tissue sections were immunohi stochemically 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 o ven heating of paraffin sections. Results. MIB-1 immunohistochemical s taining showed significant differences in mean values between 65 patie nts (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 o f 80% or less MIB-1 positively stained cells. A combined approach, usi ng the absolute volume of embryonal carcinoma per patient (< 2 mi) and MIB-1 immunostaining (less than or equal to 80%) was able to define a group of 30% of all patients who were at extremely low risk for occul t metastatic disease. Conclusions. MIB-1 immunostaining in combination with histopathology aided in defining a law risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk fo r metastasis. The risk factors need to be tested in a prospective clin ical trial to determine if they are potentially useful in assigning th erapy to individual patients.