Chromosomal Deletions at 6q, 8p, and 13q in the Early Development of Prostate Cancer
H Takahashi, M Nakano, M Furusato, H Hano. The Jikei University School of Medicine, Minato-ku, Tokyo, Japan
Background: Certain genetic alterations and accumulation are strongly associated with prostate cancer progression including metastasis. Previously, chromosomal deletions/alterations at 6q, 8p, and 13q have been reported to be important at cancer progression stage and metastasis. On the other hand, little is known for the early cancer development from pre-clinical/microscopic stage to the clinically-evident cancer.
Design: A total of 184 microscopic cancers (MC) defined as limited within a 3 mm circle and corresponding 82 clinically-evident cancer (CC) nodules were selected from radical prostatectomy specimens. Tumor volumes (TV) of MC and CC were calculated and grades were evaluated by Gleason scoring system. Thirteen microsatellite loci at 6q16-22, 8p2223, 13q14, 21 and 33 were evaluated for loss of heterozygosity (LOH). Immunohistochemistry was simultaneously performed to detect expression of alpha-methylacyl co-A racemase (AMACR).
Results: Average TV of MC was 1.26 mm3, and range was 0.03211.77 mm3. Average TV of CC was 3024.7 mm3, and range was 4213 816 mm3. The results are summarized in Table 1. Frequencies of LOH at 6q1621, 6q22, 8p23.1, 8p23.2, 13q14 were significantly higher in CC (30.9%, 40.5%, 12%, 8.7% and 20.6%) than in MC (1.0%, 2.7%, 2.9%, 1.1% and 5.4%). The results were summarized in Table 2. No significant differences of AMACR expression were detected between 2 groups (positive rate: 93.4% in MC, 100% in CC).
Table 1 TV and GSGS, Gleason score; MC, microscopic cancer; CC, clinically-evident cancer
|Average TV (mm)||Range (mm)||GS7||GS8|
Table 2 LOH frequencyLOH, loss of heterozygosity; MC, microscopic cancer; CC, clinically-evident cancer
|MC (%)||CC (%)||p|
|6q16-21||1/100 (1)||17/55 (30.9)||0.001|
|6q22||2/74 (2.7)||17/42 (40.5)||0.001|
|8p22||1/34 (2.9)||5/24 (20.8)||0.072|
|8p23.1||2/104 (1.9)||6/50 (12)||0.015|
|8p23.2||1/90 (1.1)||5/57 (8.7)||0.033|
|13q14||6/111 (5.4)||13/63 (20.6)||0.004|
|13q21||0/16 (0)||1/10 (10)||0.385|
|13q33||1/37 (2.7)||2/22 (9)||0.549|
Conclusions: Chromosomal deletions at 6q1621, 6q22, 8p23.1, 8p23.2, 13q14 are important events not only for cancer progression/metastasis but also for cancer development from pre-clinical stage to be clinically evedent. Deletions at 13q21 and 33 seems to be less important for this transition.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 97, Wednesday Morning