A FISH Assay for Detection of Excess Chromosome 12p Material To Distinguish Germ Cell Tumors from Somatic Carcinoma
Robin M Elliott, Mamta K Rao, Kristina Wang, Hikmat Al-Ahmadie, Yingbei Chen, Samson W Fine, Anuradha Gopalan, Satish K Tickoo, Suresh C Jhanwar, Victor E Reuter. Memorial Sloan-Kettering Cancer Center, New York
Background: The diagnosis of metastatic or primary extragonadal germ cell tumors (GCT) presents a unique challenge for the surgical pathologist since these tumors can mimic other tumor types. Because the treatments of GCTs vary drastically from those of the entities they mimic, there is a need for a laboratory test that can distinguish them. Excess chromosome 12p material, especially as i12p, is a recurrent abnormality in GCTs that would presumably not be detected in somatic tumors. In this study, we attempt to distinguish a set of GCTs from high grade somatic carcinoma (CA) using a new FISH assay.
Design: The set of GCTs consisted of 3 embryonal carcinomas (EC), 3 seminomas, 1 yolk sac tumor (YST), 2 immature teratomas, and 1 teratoma with secondary somatic malignancy in the form of carcinoma. The set of CAs consisted of 3 colonic adenoCAs, 3 urothelial CAs, 2 pulmonary adenoCAs, 1 pulmonary squamous cell CA, and 1 renal cell CA. FISH was performed on 5 μ sections prepared from formalin-fixed, paraffin-embedded tissue. Two cytogenetic technologists, blinded to the histologic diagnoses, performed the FISH analysis.
Four probes were used: ETV6 (12p13), CEP (12p11.1-12q11), CHOP(12q13) and MDM2(12q13). A sample was considered positive if:
>10% of cells had i12p, indicated by a doublet ETV6 signal with one CEP signal,
5-10% of cells had i12p and demonstrated an excess of ETV6 relative to 12q signals (CHOP and MDM2),
>10% of cells had excess 12p material without i12p, indicated by excess ETV6 relative to 12q signals.
Results: Of the 10 GCTs, FISH analysis detected excess 12p material in 7 cases. The positive cases included 3 ECs, 2 seminomas, the YST, and the teratoma with secondary somatic malignancy in the form of carcinoma. The 3 GCTs negative for excess 12p were a seminoma and two immature teratomas. Of the 10 CAs, FISH detected excess 12p material in 3 cases: two colonic adenoCAs and the pulmonary squamous cell CA.
Conclusions: 1. The sensitivity of this FISH assay for the detection of GCT is 70%, which is comparable to prior studies.
2. False negatives consisted of teratoma and seminoma, both of which have been shown to have a lower frequency of 12p excess than other GCT types.
3. Even when FISH probes specific for 12p and 12q loci are used, there is a high false positive rate (30%).
4. Specific types of high grade CA with a known propensity for genomic instability, such has colonic adenoCA, may have a higher frequency of 12p excess than has been previously appreciated. If these entities can be excluded, the false positive rate may be reduced.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 137, Monday Afternoon