PAX-2 in the Diagnosis of Primary Renal Tumors

Özcan, Ayhan; Zhai, Jim; Hamilton, Candice; Shen, Steven S.; Ro, Jae Y.; Krishnan, Bhuvaneswari; Truong, Luan D.

doi:10.1309/ajcpm7dw0xfhdhny

Cited by 52 publications

(7 citation statements)

References 32 publications

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“…The minimal PAX2 labeling we saw in our cases is more difficult to explain but may represent a more exaggerated effect of fixation on this marker, which we and others have found to be less sensitive than PAX8. 22 Although PAX8 and RCC marker antigen have not been studied in the t(6;11) RCC by other groups, we note that Rao et al 7 did not find CD 10 labeling in their small series of t(6;11) RCC, which differs from our results.…”

Section: Discussioncontrasting

confidence: 99%

t(6;11) Renal Cell Carcinoma (RCC)

Smith¹,

Illei²,

Allaf³

et al. 2014

American Journal of Surgical Pathology

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Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Uro-logical Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cath-epsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that metastasize.

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Section: Discussioncontrasting

confidence: 99%

t(6;11) Renal Cell Carcinoma (RCC)

Smith¹,

Illei²,

Allaf³

et al. 2014

American Journal of Surgical Pathology

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“…PAX2 and PAX8 are lineage restricted transcription factors that are known to be expressed in the renal and Müllerian systems, 13,26,29,30,35 and have been found to be expressed in most clear cell and papillary RCC. We found that 14 of 21 Xp11 translocation RCC showed nuclear labeling for PAX2, whereas 16 of 21 showed nuclear labeling for PAX8.…”

Section: Resultsmentioning

confidence: 99%

“…These include tissue-specific transcription factors such PAX2 and PAX8, 13,26,29,30 along with cytoplasmic differentiation markers such as hypoxia-inducible protein 2 (HIG2) 34 and carbonic anhydrase 9 (CA IX). 15,33 Some of these markers have been shown to differentially label the common adult subtypes of renal cell carcinoma, which are clear cell, papillary, and chromophobe RCC.…”

mentioning

confidence: 99%

Xp11 Translocation Renal Cell Carcinoma (RCC): Extended Immunohistochemical Profile Emphasizing Novel RCC Markers

Argani

Hicks

Marzo³

et al. 2010

American Journal of Surgical Pathology

178

136

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Xp11 translocation renal cell carcinoma (RCC) harbor various TFE3 gene fusions, and are known to underexpress epithelial immunohistochemical (IHC) markers such as cytokeratin and EMA relative to usual adult type RCC; however, their profile in reference to other IHC markers that are differentially expressed in other subtypes of RCC has not been systematically assessed. Few therapeutic targets have been identified in these aggressive cancers. We created 2 tissue microarrays (TMA) containing five 1.4-mm cores from each of 21 Xp11 translocation RCC (all confirmed by TFE3 IHC, 6 further confirmed by genetics), 7 clear cell RCC (CCRCC), and 6 papillary RCC (PRCC). These TMA were labeled for a panel of IHC markers. In contrast to earlier published data, Xp11 translocation RCC frequently expressed renal transcription factors PAX8 (16/21 cases) and PAX2 (14/21 cases), whereas only 1 of 21 cases focally expressed MiTF and only 5 of 21 overexpressed p21. Although experimental data suggest otherwise, Xp11 translocation RCC did not express WT-1 (0/21 cases). Although 24% of Xp11 translocation RCC expressed HIF-1α (like CCRCC), unlike CCRCC CA IX expression was characteristically only focal (mean 6% cell labeling) in Xp11 translocation RCC. Other markers preferentially expressed in CCRCC or PRCC, such as HIG-2, claudin 7, and EpCAM, yielded inconsistent results in Xp11 translocation RCC. Xp11 translocation RCC infrequently expressed Ksp-cadherin (3/21 cases) and c-kit (0/21 cases), markers frequently expressed in chromophobe RCC. Using an H-score that is the product of intensity and percentage labeling, Xp11 translocation RCC expressed higher levels of phosphorylated S6, a measure of mTOR pathway activation (mean H score = 88), than did CCRCC (mean H score = 54) or PRCC (mean H score = 44). In conclusion, in contrast to prior reports, Xp11 translocation RCC usually express PAX2 and PAX8 but do not usually express MiTF. Although they may express HIF-1α, they only focally express the downstream target CA IX. They inconsistently express markers associated with other RCC subtypes, further highlighting the lack of specificity of the latter markers. TFE3 and Cathepsin K remain the most sensitive and specific markers of these neoplasms. Elevated expression of phosphorylated S6 in Xp11 translocation RCC suggests the mTOR pathway as an attractive potential therapeutic target for these neoplasms.

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“…U imunohistohemijskom nalazu svih slu~ajeva tu-mora obuhva}enih našom studijom, dominiralo je citoplazmatsko bojenje, što iznenadjuje, budu}i da se Pax-2, kao transkripcioni faktor, dominantno ispoljava u jedru. Rezultati studije bi se mogli objasniti specifi~noš}u teh-nike imunohistohemijskog bojenja na Pax-2 antigen i po-sledice tkivne endogene avidin-vezuju}e aktivnosti ili ne-specifi~nosti sekundarnog antitela, polimer kompleksa ili drugog relevantnog te-hni~kog faktora, što je u skladu sa studijom Ozcan i saradnika 7 . Pored bubre'nih neoplazmi, ekspresija Pax-2 je uo~ena i u limfomu bubrega.…”

Section: Diskusijaunclassified

“…U adultnom periodu mo'e do}i do ponovne aktivacije Pax-2 transkripcionog faktora, u procesima epitelno-mezenhimne transfor-macije (EMT), proliferacije i transformacije tubularnog epitela i nastanka bubre'ne neoplazme 6 . S obzirom da neoplasti~na transformacija, na gore po-menut na~in, ponavlja proces organogeneze, tumori mogu ispoljiti antigene organ specifi~nih transkripcionih fakto-ra, medju njima i Pax-2 antigen, koji mogu poslu'iti kao zna~ajan dijagnosti~ki marker 7 . Mali je broj radova koji se bavio ispitivanjem u~estalosti ispoljavanja Pax-2 antigena medju razli~itim histološkim tipovima tumora bubrega 8 Imunohistohemijsko bojenje je uradjeno posle obrade tkivnih uzoraka u mikrotalasnoj rerni, u citratnom puferu pH 6.0, radi demaskiranja antigena na parafinskim presecima debljine 5µm, nakon deparafinizacije i dehidratacije.…”

unclassified