Diagnostic Utility of Detecting 12p Alterations by Fluorescence In Situ Hybridization in Ovarian Germ Cell Tumors
WR Sukov, JC Cheville, AW Carlson, GL Keeney, RP Ketterling. Mayo Clinic, Rochester, MN
Background: Germ cell tumors (GCT) comprise nearly 20% of primary ovarian tumors and can be histologically heterogeneous, often displaying features overlapping with other primary ovarian tumors. Given that patient treatment and prognosis varies greatly depending on tumor type, an accurate diagnosis is critical. Alterations of chromosome 12 including duplication of 12p and formation of isochromosome 12p (iso(12p)) have been shown to be recurrent genetic features of testicular GCT, present in 60-80% of cases. Iso(12p) has also been detected in a subset of ovarian GCT. However, the diagnostic utility of detecting 12p alterations in differentiating ovarian GCT from other ovarian tumors has not been formally investigated.
Design: After IRB approval, formalin-fixed, paraffin-embedded tissue was collected from 20 primary ovarian GCT, 10 ovarian carcinomas, 7 sex cord stromal tumors, 4 ovarian large B-cell lymphomas, 20 testicular seminomas (positive control) and 25 normal ovaries (negative control). A novel dual-color FISH probe strategy was used to identify structural and/or numerical alterations of chromosome 12p. Three clones were used to build a 390 kb FISH probe mapping to 12p11.21. This homebrew probe was used in conjunction with a chromosome 12 centromeric probe (Abbott Molecular, Abbott Park, IL). This probe cocktail allowed interrogation of chromosome 12 centromere status relative to the status of the 12p arm. FISH analyses were conducted in a blinded fashion.
Results: In testicular seminomas, FISH showed iso(12p) in 11 cases, 12p gain in 4 cases, and polyploidy of chromosome 12 in 5 cases. Table 1 shows results of FISH for primary ovarian tumors. Iso(12p) was identified in 10 of 20 (50%) ovarian GCTs. No ovarian tumor showed gain of 12p. No chromosome 12 alterations were seen in normal ovaries.
|iso(12p)||Polyploidy Chr 12||Diploid Chr 12|
|Ovarian carcinoma, clear cell||2/4||1/4||1/4|
|Ovarian carcinoma, endometrioid||1/4||3/4||0/4|
|Ovarian carcinoma, mixed serous/ endometrioid||0/1||1/1||0/1|
|Ovarian carcinoma, mixed serous/ clear cell||1/1||0/1||0/1|
|Sex cord stromal tumor||0/7||1/7||6/7|
Conclusions: The present findings suggest that iso(12p) is a common finding in ovarian GCT and supportive of the diagnosis. However, demonstration of iso(12p) pattern by FISH is not a finding specific for GCT and can be demonstrated in other primary ovarian tumors, especially clear cell carcinoma.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 165, Monday Morning