Utility of PAX8 and PAX2 Immunohistochemistry in the Diagnosis of Renal Cell Carcinoma in Cytology Specimens.
Stewart M Knoepp, Lakshmi P Kunju, Michael H Roh. University of Michigan Medical School, Ann Arbor
Background: The diagnosis of metastatic renal cell carcinoma (RCC) in cytology specimens may be difficult to confirm on the basis of cytomorphology alone. Often, immunohistochemistry serves as an important adjunct in confirming this diagnosis. Recently, PAX2 was shown to be useful in this regard. As there are no reports to date that examine the role of PAX8 in the cytologic diagnosis of RCC, we sought to investigate and compare the diagnostic utility of PAX8 and PAX2.
Design: First, the performance of PAX8 immunohistochemistry was verified using a tissue microarray (TMA) composed of 30 clear cell RCCs, 17 papillary RCCs, and 7 chromophobe RCCs. Next, the pathology database was searched from 2000 to 2010 for cases in which a cytologic diagnosis of RCC was rendered in patients with histologically confirmed disease based on primary resections and/or biopsies of metastases. Twenty-four cases (17 fine needle aspirates and 4 effusions) were identified. The associated histologic diagnoses were clear cell RCC (14 cases), papillary RCC (4 cases), papillary RCC with sarcomatoid transformation (1 case), pure sarcomatoid RCC (1 case), and RCC of unknown subtype (4 cases). Immunohistochemistry using rabbit polyclonal antibodies directed against PAX8 (1:200 dilution; ProteinTech, Chicago, IL) and PAX2 (1:100 dilution; Invitrogen, Camarillo, CA) was performed on cell block sections prepared from these cases.
Results: PAX8 immunoreactivity was seen in at least 10% of the tumor cells in all cases of RCC in the TMA. Next, PAX8 positivity was seen in 21 (88%) of 24 cytology cases. In 17 of the 21 PAX8(+) cases, greater than 50% of the tumor cells exhibited nuclear immunoreactivity for PAX8. In the other four PAX8(+) cases, at least 10% of the tumor cells were immunopositive. For comparison, the 24 cytology cases were also immunostained for PAX2. PAX2 positivity was seen in 20 (83%) of 24 cases. In 14 of these 20 PAX2(+) cases, over 50% of the tumor cells were PAX2(+). In the other six PAX2(+) cases, at least 10% of the tumor cells were immunoreactive for PAX2. Overall, immunoreactivity for both PAX8 and PAX2 was seen in 19 (79%) of 24 cases. Finally, positivity for either of the two markers was detected in 22 (92%) of the 24 cases.
Conclusions: Our results demonstrate that both PAX8 and PAX2 are useful markers for identifying metastatic RCC in cytology specimens. While PAX8 shows a slight increase in sensitivity over PAX2 in RCCs, the highest sensitivity and therefore greatest utility lies in using both markers for confirming a diagnosis of RCC.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 81, Wednesday Afternoon