Microsatellite instability and loss of heterozygosity in prostatic carcinomas: Comparison of primary tumors, and of corresponding recurrences after androgen-deprivation therapy and lymph-node metastases
H. Rohrbach et al., Microsatellite instability and loss of heterozygosity in prostatic carcinomas: Comparison of primary tumors, and of corresponding recurrences after androgen-deprivation therapy and lymph-node metastases, PROSTATE, 40(1), 1999, pp. 20-27
BACKGROUND. The molecular mechanisms leading to prostate cancer progression
are poorly understood. In particular, those changes which are responsible
for androgen-independent growth and metastatic spread in prostate cancer ar
e an issue of current investigations.
METHODS. To gain more insight into these processes, paired microdissected s
amples from both untreated, locally advanced primary tumors (n = 20) and re
currences (n = 20) after conventional androgen-deprivation therapy (ADT) we
re analyzed retrospectively for microsatellite instability (MSI) and loss o
f heterozygosity (LOH) at nine loci on chromosomes 8, 18, and X by polymera
se chain reaction. In parallel, 12 prostatic carcinomas treated by radical
prostatectomy and nine corresponding lymph-node metastases were analyzed in
the same way.
RESULTS. The group treated with ADT showed a total of 10 MSI in 7 of the pr
imary tumors (35%): 4 of these (20%) at one locus, and 3 of these (15%) at
two loci. In the recurrences, MSI was observed in 4 cases (20%): 3 of these
at one locus (15%), and 1 of these (5%) at two loci. LOH was found in 8 ca
ses (40%) before as well as after ADT. In the radically resected carcinomas
, MSI could be detected at two chromosomal loci in one of the primary tumor
s (8%) and in one of the metastases (11%); LOH was found in 2 primaries (16
%) and 3 metastases (33%).
CONCLUSIONS. Although MSI can be found in advanced prostatic carcinomas, it
apparently does not play a major role in the progression of prostate cance
r regarding androgen-independent growth or lymphogenous spread. (C) 1999 Wi
ley-Liss, Inc.