PRIMARY MEDIASTINAL AND TESTICULAR SEMINOMAS - A COMPARISON OF K-RAS-2 GENE SEQUENCE AND P53 IMMUNOPEROXIDASE ANALYSIS OF 26 CASES

Primary mediastinal seminomas (MS) are rare tumors. Histologically, th ey are similar to their counterpart in the gonads. The survival rate h as varied from 50% to 85% in different series. However, large series o f these tumors primarily in the mediastinum are lacking. At the molecu lar level, a few reports document K-ras mutations in up to 40% of test icular seminomas (TS), localized predominantly to codon 12. Reports on TS p53 immunohistochemistry (IHC) range from negative to overexpressi on approaching 90% of cases, and by sequence analysis one small series showed a 23% mutation rate. To date, no analyses have been performed for either K-ras mutations or p53 immunohistochemical expression in pr imary MS. The authors studied 13 cases each of primary MS and TS from archival formalin-fixed, paraffin-embedded sections in which adequate tumor sampling and clinical history, including serological studies, an d histological, histochemical, and LHC staining, were performed to con firm the diagnosis. p53 immunoperoxidase staining using citrate buffer /microwave antigen retrieval was performed. Topographic genotyping was performed on 5-mu m-thick tissue sections up to 17 years old, in whic h the neoplastic cell population was sampled. Additionally, multiple s ites within a given cases were sampled to determine clonality of the t umor cell population. Polymerase chain reaction and subsequent sequenc e analysis of the K-ras-2 exon-1 gene was used for mutation analysis. Focal weak staining with p53 MC was observed in 4 of 13 (31%) MS and 1 0 of 13 (77%) TS cases, with all remaining cases being negative (P < . 05). Only one MS case (8%) showed K-ras mutation (codon 13 GGC > GAG; glycine > aspartate), which is in contrast to 2 of the TS cases (15%), showing codon 12 mutations. All the remaining cases were wild type. T herefore, primary mediastinal seminomas appear to be different in thei r K-ras sequence and p53 immunostain profile from TS. Codon mutation t ype may be useful in determining primary versus metastatic origin of a mediastinal seminoma.