External beam radiotherapy (EBRT) suppressed prostate stem cell antigen (PSCA) mRNA expression in clinically localized prostate cancer.
BACKGROUND
Prostate stem cell antigen (PSCA), a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens, is overexpressed in human prostate cancer (PCa). Our recent data indicated that complete androgen ablation could significantly suppress PSCA mRNA expression in primarily organ-confined PCa. The effect of external beam radiotherapy (EBRT), one of the curative treatment options for localized PCa, on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after EBRT, and further evaluate the prognostic value of PSCA in this disease.


METHODS
Between January 1999 and June 2005, 87 men with clinically localized adenocarcinoma of the prostate received only EBRT with a total dose of 65-70 Gy for 6.5-7 weeks. PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue and post-treatment biopsy tissue of all 87 men, respectively. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after EBRT were analyzed using the Student's t-test. Twenty-four to seventy months continuous follow-up studies after treatment were performed and aimed at assessing the correlation of PSCA mRNA expression level with biochemical relapse and/or distant metastases from the cancer.


RESULTS
The percent of cells positive for PSCA mRNA by ISH labeling declined from 71.2% (0-93%) +/- 9.7% before EBRT to 30.7% (0-90%) +/- 5.3% after EBRT (P<0.001). Before EBRT, 81 of 87 cases (93.1%) were positive for PSCA mRNA labeling, however, after EBRT the percentage of positive reactivity of PSCA mRNA was decreased to 62 of 81 cases (76.5%), in which 59 men (95.2%) were found without biochemical relapse or distant metastases on follow-up. This decline in PSCA mRNA labeling was directly proportional to higher pretreatment serum PSA level, higher tumor grade (Gleason score), and higher clinical T stage. The rest 19 cases had the increased percentage of cells positive for PSCA mRNA after EBRT, in which 15 cases developed biochemical relapse and/or distant metastases from tumor on follow-up.


CONCLUSIONS
We found that EBRT for PCa can significantly suppress PSCA mRNA expression and the elevated PSCA mRNA level after EBRT may be a clinically adverse predictor for tumor progression.
Zhigang
Zhao
Z
Department of Urology, The Second Affiliated Hospital, Shantou University Medical College, Guangdong Province, China. zgzhaodr@yahoo.com.cn
Wenlu
Shen
S
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002452:Cell Count; D018450:Disease Progression; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000378:metabolism*; D020728:Transurethral Resection of Prostate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen