[992] Overexpression of AKT in Prostate Cancers and Association with an Agressive Tumor Type

H Takahashi, T Yamamoto, M Furusato, S Egawa, H Hano. The Jikei University School of Medicine, Tokyo, Japan

Background: AKT is a component of the PI-3 kinase pathway and is activated by phosphorylation. It is a key regulator of many signal transduction pathways and overexpression has been noted in many types of cancer. Little is known about this phenomenon and clinical correlation in prostate cancer.
Design: A total of 101 cancer foci and 38 HGPIN were selected from our prostatectomy series. The cancer included 53 clinically-evident tumors (index tumor: IT), and 48 microscopic tumors (MT, the largest diameter <2mm). Immunohistochemistry was performed with anti-AKT (phosphorylation form specific) and expression was evaluated. Inensity and distribution were evaluated as grade 0 (none), 1 (weak/<10% of the tumor), 2 (intermediate/10-49%), 3 (strong/>50%), 4 (very strong/>50%). Grades 2-4 were designated as expression+. Grade 4 was defined as overexpression+. The data were compared with stage (pT), Gleason score, and PSA-free survival.
Results: Frequency of expression+ was significantly higher in IT than in MT (51% vs. 9.1%: p<0.05). Nine cases showed overexpression in IT and none in MT/HGPIN.

Tabel 2 Immunohistochemistry of AKT

	0	1	2	3	4
IT (n=53)	10 (18.8%)	15 (28.3%)	8 (15.1%)	11 (20.8%)	9 (17.0%)
MT (n=48)	34 (70.8%)	10 (20.8%)	3 (6.3%)	1 (2.1%)	0
HGPIN (n=38)	38 (100%)	0	0	0	0

IT vs. MT, p<0.05; IT vs. HGPIN, p<0.05

Nine cases with overexpression+ showed significantly higher stage and grade (3 cases: pT2c, 4: pT3a, 2: pT3b; 2: 3+4=7, 5: 4+3=7, 2: 4+5=9) than cases with overexpression- (10 cases : pT2a-b, 24: pT2c, 5: pT3a, 5: pT3b; 11:3+3=6, 25: 3+4=7, 4: 4+3=7, 2: 4+4=8, 2: 4+5=9).

Table 2 pT and GS in overexpression+ and - tumors

pT	T2a-b	T2c	T3a	T3b
Overexpression+	0 (0%)	3 (33.3%)	4 (44.5%)	2 (22.2%)
Overexpression-	10 (22.7%)	24 (54.5%)	5 (11.4%)	5 (11.4%)
GS	3+3=6	3+4=7	4+3=7	8-10
Overexpression+	0 (0%)	2 (22.2%)	5 (55.6%)	2 (22.2%)
overexpression-	11 (25.0%)	25 (26.9%)	4 (9.1%)	4(9.1%)

overexpression+ vs. - in pT and GS, p<0.05

In the follow-up (36 months), 4/8 cases with overexpression+ showed biochemical failure (0 month-24 months).
Conclusions: Overexpression of phosphorylated AKT is suggested to play an important role in the tumor progression and indicating an aggressive tumor type. Reversely, it is not significant in the pre-clinical prostate cancer and HGPIN.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 100, Wednesday Morning