Prognostic relevance of prothymosin-alpha expression in human upper urinary tract transitional cell carcinoma.
OBJECTIVE
To investigate the prognostic role of prothymosin-alpha (PTMA) expression in human upper urinary tract transitional cell carcinoma (UUT-TCC).


METHODS
Paraffin-embedded tissues were collected from 91 patients with UUT-TCC and from 15 paired normal renal cortex and 13 paired urothelial walls. The primary antibody for PTMA (2F11) used was validated in 4 human urothelial cancer cell lines before assessing the surgical specimen. Immunohistochemistry was then conducted to determine the expression intensity of PTMA, the calculation of immunostaining density using imaging analysis, and for immunostaining localization. The correlates with clinicopathologic characteristics and patient survival were explored.


RESULTS
The expression intensity of PTMA demonstrated a significant enhancement of PTMA expression in UUT-TCCs compared with both paired normal tissues (P = .0002 and P = .0004 for UUT-TCC vs the urothelial wall and vs the renal cortex, respectively). As for the localization of PTMA immunoreactivity, of the 91 tumor specimens, 33 (36.3%) were cytoplasmic PTMA-expressing, 51 (56.0%) were nuclear PTMA-expressing, and 7 (7.7%) were PTMA-negative tumors. On univariate and multivariate analyses, PTMA expression localization was the sole independent prognostic indicator for recurrence-free survival (hazard ratio 4.90, 95% confidence interval 1.73-13.9; P = .003), although pathologic staging was an independent prognostic indicator for both progression-free survival (hazard ratio 22.6, 95% confidence interval 2.56-198; P = .005) and disease-specific overall survival (hazard ratio 5.60, 95% confidence interval 1.48-21.2; P = .011). The limitations of our study included small patient numbers and short follow-up.


CONCLUSIONS
The results of our study have shown that PTMA is overexpressed in UUT-TCCs and that cytoplasmic PTMA expression can provide significant prognostic information for subsequent tumor recurrence in the residual urinary tract after nephroureterectomy.
Jou
Yeong-Chin
YC
Department of Urology, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
Tung
Chun-Liang
CL
Tsai
Yuh-Shyan
YS
Shen
Cheng-Huang
CH
Syue-Yi
Chen
C
Shiau
Ai-Li
AL
Tsai
Hsin-Tzu
HT
Wu
Chao-Liang
CL
Tzai
Tzong-Shin
TS
D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D011498:Protein Precursors / Q000096:biosynthesis*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000601:surgery*
D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin