THE CORRELATION OF P53 PROTEIN EXPRESSION WITH PROLIFERATIVE ACTIVITYAND OCCULT METASTASES IN CLINICAL STAGE-I NONSEMINOMATOUS GERM-CELL TUMORS OF THE TESTIS

Sixty-nine cases of clinical Stage I non-seminomatous germ cell tumors (NSGCT) of the testis were immunostained for the protein product of t he p53 tumor suppressor gene using a microwave-based antigen retrieval method. It was assumed that the immunohistochemical detection of the p53 protein corresponded to a point mutation in the p53 gene, the wild -type p53 protein turning over too rapidly to be detected by routine i mmunohistochemical techniques. The results of p53 staining were then c ompared with the results, on the same paraffin tissue blocks, of S-pha se analysis, as determined by flow cytometry, and the percentage of ne oplastic cells exhibiting immunohistochemical positivity for prolifera ting cell nuclear antigen (PCNA). Thirty-four of 69 (49%) of the clini cal Stage I NSGCT exhibited p53-positivity as strong, but focal, intra nuclear positivity. Both the mean total S-phase and the mean percentag e of PCNA-positive neoplastic cells were significantly higher in the p 53-positive cases (27.8% and 89.6%, respectively) compared with the p5 3-negative cases (17.6% and 66.1%, respectively). Stratification of ca ses into high (greater than or equal to 76%) and low categories for PC NA values correlated significantly (P < 0.0005) with p53-positivity an d negativity, respectively, by chi(2) analysis. The positive associati on of p53 protein expression with higher proliferative indices in NSGC T of the testis is consistent with the observation of p53 mutations co rrelating with markers of increased tumor aggressiveness in other type s of neoplasia. None of these parameters (p53 positivity, high PCNA va lues, or high total S-phase), however, correlated significantly with o ccult metastases in these patients.