Renal Cell Carcinoma
The use of IHC in the setting of renal cell carcinoma (RCC) usually falls into one of two categories: (1) carcinoma of unknown primary, or (2) differentiation of RCC subtypes. Dependent upon which category one is in dictates what type of panel to utilize.
RCC vs. Other Malignancy
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>80% expression in RCC
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>80% expression in RCC
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CK7/CK20
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Both typically negative in clear cell RCC
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>95% expressión in convencional clear cell RCC
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>85% expression in clear cell and papillary subtypes
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Variable but usually positive (author’s experience)
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Positive
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RCC Conventional Clear Cell type is one of a limited differential with co-expression of vimentin and cytokeratin.
RCC Subtype Differentiation
IHC may be helpful in sub-typing a RCC tumor. This usually occurs in the setting of differentiating between a chromophobe RCC and a conventional clear cell RCC with eosinophilic cytoplasm. The best way to confirm a clear cell RCC is to take more sections, and definitively identify clear cell areas. Unfortunately, on small biopsies this may not be possible, and IHC provides helpful clues.
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Negative in chromophobe RCC/oncocytoma, and >85%+ in clear cell RCC.
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Usually expressed in most RCCs, but literature varies widely. CAM5.2 probably better consistency and sensitivity.
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>80% + in chromophobe RCC/oncocytoma, and negative (<5%+) in clear cell RCC.
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Oncocytomas are usually negative for CK7, while chromophobe RCC is often positive.
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Almost all oncocytomas and chromophobe RCCs show expression of E-Cadherin. Clear cell and papillary RCCs are typically negative. Xp11.2 translocation RCC are usually positive.
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TFE3 is a specific marker for Xp11.2 translocation renal cell carcinomas, and is expressed in >90% of such cases.
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As a general rule of practice in IHC, it is best to have both positive and negative markers for differentiation.
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IHC Stain
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RCC
Clear Cell
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RCC
Papillary
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RCC
Chomophobe
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RCC
Xp11.2
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94-100%
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67-93%
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+/- 0-72%
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+ >90%
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0-37%
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80-87%
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73-86%
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17%
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=
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=
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=
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N/A
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35% (varies)
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82%
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16%
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11%
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87%
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100%
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=
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66%
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92%
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87%
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+/- 0-82%
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98%
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87%
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83%
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72-85%
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87-95%
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0-91%
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0-5%
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0-13%
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82-100%
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88%
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>90%
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>90%
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Negative
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Negative
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Positive
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68%
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AE1/AE3 has varying positivity in the literature. Part of this is probably due to that AE1/AE3 lacks CK18, which is expressed by most RCCs. Other CKs have varying expression. CAM5.2 is recommended over AE1/AE3.
Differential Diagnosis
Adrenocortical Carcinoma: AE1/AE3 -, EMA -, RCC Ma., Inhibit +, Calretinin +
Angiomyolipoma: MART-1 +, HMB-45 +, Tyrosinase +, Smooth Muscle Markers +, Cytokeratins -, EMA –
Photomicrographs
References
Arch Path Lab Med – Vol. 135, Jan. 2011 (Truong & Shen).
Pan, CC. “Differential Immunoprofiles of Hepatocellular Carcinoma, Renal Cell Carcinoma, and Adrenalcortical Carcinoma.” Appl Immunohistochem Mol Morphol. Vol. 13, No. 4, Dec. 2005.
Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. [edited by] DJ Dabbs. 3rd Edition. Elsevier, 2010.
Shen, SS. “Role of Immunohistochemistry in Diagnosing Renal Neoplams: When Is It Really Useful?”Arch Pathol Lab Med, Vol. 136, April 2012. pp. 410-417.
Camparo, P., Vasiliu, V., Molinie, V., Couturier, J., Dykema, K. J., Petillo, D., et al. (2008). Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. The American Journal of Surgical Pathology, 32(5), 656–670. doi:10.1097/PAS.0b013e3181609914