[1046] How Immunohistochemistry Can Help To Identify Renal Tumors Associated with SDHB Syndrome

Beatriz A Walter, Vladimir A Valera, Karel Pacak, Marston Linehan, Maria J Merino. NCI, NIH, Bethesda

Background: Renal cell carcinoma (RCC) is composed of several histologic subtypes. While the majority occur sporadically, about 5% are associated with hereditaries syndromes. Lately, our understanding of RCC-predisposing syndromes has improved and genes associated with specific tumors have been discovered. However, there are no specific IHC stains to assist in the identification of each tumor type. Germline mutations in genes that code for the succinate dehydrogenase complex subunits (SDHB, SDHC and SDHD) are associated with a high risk of head and neck paragangliomas, extra-adrenal pheochromocytomas and RCC. SDHB protein by IHC can definitely assist in identifying renal tumors and patients that are part of the SDHB syndrome.
Design: Ninety tumors representing the wide histologic spectrum of RCC were evaluated, including 10 oncocytomas, 36 clear cell RCC (ccRCC) (10 with hx of VHL), 10 chromophobe RCC, 5 Hybrid tumors with BHD mutation, 13 HLRCC, 3 Papillary type and 13 cases of RCC with known SDHB mutation. Complete sections of the tumors were used to evaluate SDHB protein expression by IHC. Two different antibodies were used to recognize different binding sites of the target protein, (N-terminal 4-150 aa) and (C-terminal 165-273 aa) (Sigma-Aldrich, USA).
Results: Ten oncocytomas and 67 RCC of different subtypes stained positive with both SDHB antibodies. Normal renal tubules showed a moderate fine granular cytoplasm staining as a control. Oncocytomas showed a stronger intensity in the cytoplasm, followed by ccRCC high Furhman grade. All the other ccRCC associated or not with VHL mutation, HLRCC and chromophobes cases were also positively stained. Hybrid tumors were intensely staining the eosinophilic cells. All of the RCC with known SDHB mutation were negative with both antibodies. These patients, ranged in age from 15 to 61 years with a female predominance. Histologically 11/13 cases (70%) showed oncocytic features with groups of clear cells; only two cases also had a spindle cell component. Most of the oncocytic cells have a unique intracytoplasmic inclusion which was confirmed by EM.
Conclusions: We concluded that IHC staining of RCC with SDHB markers can be of great help to identify patients that can be part of the SDHB syndrome. All our cases stained negative by IHC with both markers, meanwhile all the different types of RCC, including tumors that are part of other hereditary syndromes stained positive. Early identification of patients with SDHB syndromes will definitely allow to improve survival by proper screening of the families.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 155, Tuesday Morning


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