Prognostic value of CD44 standard, variant isoforms 3 and 6 and -catenin expression in local prostate cancer treated by radical prostatectomy.
OBJECTIVE
The clinical and histological data of prostate cancer patients were compared with the expression of CD44 standard (CD44s), variant isoforms CD44v3, CD44v6 and alpha-catenin. The prognostic value of these adhesion molecules was also analysed.


METHODS
We analysed the clinical and histological data of 87 prostate cancer patients treated by radical prostatectomy in two Finnish hospitals. The mean (SD) age of the patients at diagnosis was 64 years (6) and the mean follow-up was 3 years (8). Immunohistochemistry was used to detect the expression of CD44s and its v3 (CD44v3) and v6 (CD44v6) isoforms and alpha-catenin.


RESULTS
The mean (SD) fractions of positively stained cancer cells were 38 (38), 10 (22), 56 (41) and 93% (17) for CD44s, CD44v3, CD44v6 and alpha-catenin, respectively. Low fractions of CD44s- and CD44v6-positive cancer cells were related to high preoperative prostate-specific antigen (PSA) levels (p<0.05 for both). Low fraction of CD44s positive cancer cells was linked with presence of seminal vesicle invasion (p = 0.07), surgical margin positivity (p = 0.09), high Gleason score (p = 0.04) and high mitotic index (p = 0. 02). Low fraction of CD44v3-positive cancer cells was related to positive surgical margins (p = 0.05), high Gleason score (p = 0.04), presence of perineural infiltration (p = 0.02) and absence of tumour-infiltrating lymphocytes (p = 0.02). Low fraction of CD44v6-positive cancer cells was related to high pT classification (p = 0.07), capsule invasion (p = 0.03), positive surgical margins (p = 0.05), high Gleason score (p = 0.008), perineural infiltration (p = 0.0001) and high mitotic index (p = 0.001). alpha-Catenin expression was not related to any of the clinicopathological variables included in this study. Gleason score (p = 0.001), pT classification (p = 0.007), perineural infiltration (p = 0.01) and the fraction of CD44v3-positive cancer cells (p = 0.04) were predictors of PSA failure in univariate analysis. pT category (p = 0. 012), Gleason score (p = 0.02) and expression of CD44v3 (p = 0.0003) were independent predictors of PSA failure.


CONCLUSIONS
The expression of CD44s, CD44v3 and CD44v6 is related to tumour differentiation. The expression of CD44v3 independently predicts PSA failure in addition to Gleason score and pT category during a short-term follow-up.
Aaltomaa
S
S
Department of Urology, Kuopio University Hospital, Kuopio, Finland. sirpa.aaltomaa@kuh.fi
Lipponen
P
P
Viitanen
J
J
Kankkunen
J P
JP
Ala-Opas
M
M
Kosma
V M
VM
D015820:Cadherins / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D020033:Protein Isoforms / Q000235:genetics; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D051178:alpha Catenin