Renal Medullary Carcinoma: Molecular, IHC, and Pathologic Correlation
Q Liu, L Wrathall, S Galli, J Vicens, WM Linehan, M Tsokos, MJ Merino. National Cancer Institute, Bethesda, MD
Background: Renal medullary carcinoma is a highly aggressive tumor occurring in patients with sickle cell hemoglobinopathy. It is characterized by advanced stage at the time of presentation and lack of response to therapy. The molecular alterations of these tumors are not well-known. Mutations/deletions of SNF5/INI1 gene and absence of expression of INI 1 have been demonstrated in a variety of tumors, such as renal rhabdoid tumors, and CNS atypical teratoid/rhabdoid tumors. In animal models, loss of hSNF5/INI1 gene predisposes to aggressive cancers. In the present study, we investigated the genetic, immunohistochemical, and pathological changes of renal medullary carcinoma and their role in diagnosis.
Design: Fifteen renal medullary carcinoma cases were collected from NCI pathology files. All cases had characteristic histologic features of renal medullary carcinoma. Immunohistochemistry of CK7, CD20, AE1/3, Vimentin, CAM5.2, CEA and INI1 were performed. Tumor and normal tissue from paraffin-embedded, histology sections were manually microdissected, and PCR-based microsatellite analysis of LOH for INI1 was performed using 5 pairs of primer sets from D22S303, D22S257, D22S345, TOP1P2, D22S310 regions on chromosome 22q.
Results: Ten patients were males and 5 females ranging age from 8-49 years (mean 26). History of sickle cell trait was obtained in 8 cases, one case had sickled RBCs in the specimen, and the sickle cell status of the remaining cases was unknown. Tumors involved predominantly the right kidney (right,11 cases; left, 4 cases). The average size of the tumor was 6 cm (1.1-15 cm); 11 cases had lymphovascular invasion; 9 cases had perirenal fat invasion; 9 cases had lymph node metastasis, 3 cases had renal vein invasion. IHC showed 9/9 cases positive for CEA; positive staining was also seen with CK20, CK7, CAM5.2, AE1/3, and Vimentin. INI1 immunohistochemistry staining was negative in all 6 cases studied similarly to 3 renal rhabdoid tumor cases and in contrast to a renal papillary carcinoma that were used as controls. Among the 9 cases tested by LOH analysis, 8 cases were found to have LOH of hSNF5/INI1 gene with varying degree of deletion.
Conclusions: Our study shows LOH of hSNF5/INI gene in the tumors, suggesting that LOH of hSNF5/INI may be involved in the pathogenesis of renal medullary carcinoma. The immunohistochemical profile reported here maybe helpful in confirming the diagnosis of these aggressive tumors.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 2:00 PM
Platform Session: Section A, Tuesday Afternoon