Expression of p21 and mutant p53 gene products in residual prostatic tumor cells after radical radiotherapy.
BACKGROUND
In a previous study, sextant core biopsies revealed residual tumor in the prostate in 37/55 investigated patients, with an average of 6.8 years after external beam radiation therapy (RRT). More than half of the biopsies exhibited Ki-67 and PCNA proliferation activity.


METHODS
The present study aims at further characterizing residual tumor cells post-RRT by investigating whether the tumor cells exhibit immunohistochemical expression of p21 and mutant p53 gene products, which reflect the state of cell cycle regulatory mechanisms.


RESULTS
Positive p53 staining was observed in 11% and p21 positivity in 47% of biopsies. The proportion of positively stained cells was low for both antigens. The staining patterns point to the existence of wild-type p53-dependent, as well as alternative pathways for p21 protein induction.


CONCLUSIONS
A low proportion of tumor cells exhibited p53 protein accumulation post-RRT. G1 arrest, as assessed by p21 immunoexpression, was demonstrated in a low percentage of tumor cells in < 50% of post-RRT biopsies, indicating that the vast majority of residual tumor cells following RRT escape the G1/S checkpoint control and propagate into S-phase, presumably with a maintained malignant potential.
Ljung
G
G
Department of Oncology, Akademiska Sjukhuset, University of Uppsala, Sweden.
Egevad
L
L
Norberg
M
M
Holmberg
L
L
Nilsson
S
S
Busch
C
C
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D001706:Biopsy; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016296:Mutagenesis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
C493956:CDKN1A protein, human; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases