Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma.
OBJECTIVE
Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome.


METHODS
Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed.


RESULTS
Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5%) demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis.


CONCLUSIONS
Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.
Horiguchi
Akio
A
Department of Clinical Research and Urology, National Saitama Hospital, Saitama, Japan.
Oya
Mototsugu
M
Uchida
Atsushi
A
Marumo
Ken
K
Murai
Masaru
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt