Differential expression of activator protein-2 isoforms in renal cell carcinoma.
OBJECTIVE
To investigate the expression of activator protein-2 (AP-2) in renal cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha), beta (beta), and gamma (gamma) are known to exhibit a highly homologous structure; however, their functions are considered to be different. AP-2 has been implicated to play a role in carcinogenesis, as well as in the development of the kidney.


METHODS
The expression of the three AP-2 isoforms, alpha, beta, and gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal growth factor receptor and erbB2 expression in 42 patients with RCC was also evaluated to investigate the correlation with AP-2 isoforms.


RESULTS
AP-2 isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP-2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably, localized small cases had a significantly greater rate of nuclear staining for AP-2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2 cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor receptor and erbB2 expression did not correlate with expression of the AP-2 isoforms.


CONCLUSIONS
AP-2 isoforms were differentially expressed in RCC, as well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and this transcription factor may be related to early carcinogenesis.
Oya
Mototsugu
M
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Mikami
Shuji
S
Mizuno
Ryuichi
R
Miyajima
Akira
A
Horiguchi
Yutaka
Y
Nakashima
Jun
J
Marumo
Ken
K
Mukai
Makio
M
Murai
Masaru
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C493673:TFAP2A protein, human; C493677:TFAP2B protein, human; C493679:TFAP2C protein, human