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.
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 are an issue of current investigations.


METHODS
To gain more insight into these processes, paired microdissected samples from both untreated, locally advanced primary tumors (n = 20) and recurrences (n = 20) after conventional androgen-deprivation therapy (ADT) were analyzed retrospectively for microsatellite instability (MSI) and loss of heterozygosity (LOH) at nine loci on chromosomes 8, 18, and X by polymerase 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 primary 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 cases (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 tumors (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 cancer regarding androgen-independent growth or lymphogenous spread.
Rohrbach
H
H
Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany. Helmut.Rohrbach@lrz.uni-muenchen.de
Haas
C J
CJ
Baretton
G B
GB
Hirschmann
A
A
Diebold
J
J
Behrendt
R P
RP
Löhrs
U
U
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D002898:Chromosomes, Human, Pair 8; D018450:Disease Progression; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D014960:X Chromosome
D000726:Androgen Antagonists