Fluorescence in situ hybridization on nuclei from paraffin-embedded tissue in low stage pure embryonal carcinoma of the testis

Ruthann I. Blough, Nyla A. Heerema, Peter Albers, Richard S. Foster

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Abstract

Approximately 30% of patients who present with clinical stage A nonseminomatous testis cancer are in fact pathologic stage B. In previous studies an increasing volume of embryonal carcinoma in the orchiectomy specimen was associated with a higher likelihood of being pathologic stage B. However, not all patients with pure embryonal carcinoma in the primary tumor were pathologic stage B. In an effort to discriminate patients with pure embryonal carcinoma in the testicular specimen relative to pathologic stage, archival specimens from patients presenting with clinical stage A pure embryonal carcinoma were examined by fluorescence in situ hybridization (FISH) with newly developed probes for chromosome arms 12p and 12q. Whole nuclei from archival material from 14 patients (six pathologic stage A, seven pathologic stage B and one stage C) with 100% embryonal carcinoma in the orchiectomy specimen were studied using bicolor FISH with chromosome arm 12p- and 12q-specific painting probes developed by chromosome microdissection. In all cases a blinded analysis showed distinct regions of 12p and 12q probe hybridization simultaneously and allowed identification of probable normal chromosomes 12, as well as regions of amplification of 12p sequences, including possible i(12p). In 5/14 specimens, a distinct and peculiar pattern of 12p hybridization was observed which resembled 12p 'disarray' or 'multifocal 12p'. Of the five specimens demonstrating multifocal 12p, four were pathologic stage B, while one was pathologic stage A. Whether the trend toward multifocal 12p predicts metastatic potential in primary testicular embryonal carcinoma will need to be assessed using a larger series of patients.

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