| basal
cells associating PIN were variably re-duced
in number and showed strong reactivity (+++),
while the secretory cells showed mo-derate
(++) reactivity. The number of immuno-labeled
stromal cells was higher than that in BPH
(Fig. 6) (Table 2). In
22 out of 28 biopsies of prostatic adeno-carcinoma
(78.5%), EGFr was identified as a diffuse
pattern of moderate expression (++) in most
of the secretory neoplastic cells. On the
contrary, high-grade carcinomas displayed
a mild (+) to moderate (++) expression.
Fre-quent stromal cells were positive for
EGFr (Fig. 7). Moderate immunoreactivity
was detected in all TCC cases (Fig. 8).
Analysis of p53 expression
All
biopsies of BPH, and low-grade PIN showed
negative reaction to p53, while 4 out of
10 high-grade PIN biopsies (40%) showed
a similar finding was reported by Yaman
et al.4, who stated that non-neoplastic
tissues were normally negative for p53,
and that a positive immunostaining meant
the presence of a point mutation in the
gene. On the contrary,Tamboli et al.7, reported
that the expression of p53 was detected
in 20% of their examined cases of BPH.
In this study no positive reaction was detected
in low-grade PIN. However, 40% of high-grade
PIN showed a moderate positive reaction
for p53. Yaman et al. reported a posi-tive
reaction of p53 in 18.2% of high-grade PIN4,
while Tamboli et al. reported that 56% of
high-grade PIN expressed p537. Phenotypic
and genotypic alterations of high-grade
PIN could be participating in the progression
to prostatic carcinoma8.
In
the current study, the expression of p53
was identified in 64.2% of adenocarcinoma
cases. Nuclear immunostaining was moderate
to strong. In the study of Yaman et al.,
the expression of p53 was detected in 16.1%
of adenocarcinoma cases4, while in the study
of Tamboli el al. 72% of their examined
prostatic cancers expressed p537. Johnson
et al. sug-gested that an accumulation of
p53 protein was infrequent in prostate cancer
and absent in high-grade PIN. They concluded
that p53 expression was infrequent in clinically
confined prostatic cancer9. However, Haussler
et al. re-ported that the expression of
p53 was confined to cancer and not found
in BPH or in PIN10.
Yaman
et al. expressed the opinion that a correlation
of p53 expression with cancer stage and
Gleason score demonstrated that there was
no statistically significant relationship
bet-ween p53 expression and these clinico-pathological
parameters and no significant association
between p53 expression and pro-gression
of the tumor4.
Myers et al. reported that EGFr reactivity
was observed in both BPH and prostatic carcinoma.
They concluded that the expres-sion of EGFr
was strongest along the basal aspects of
BPH cells11. In our study, the expression
of EGFr was observed in most examined cases
of BPH and low-grade PIN. EGFr immunostaining
was strictly localized in basal cells and
in lateral plasma membranes of secretory
cells. Also, we found focal weak expression
in stromal cells. Cohen et al. reported,
though, that only epithelial cells of normal
subjects and BPH cases expressed EGFr, but
not stromal cells12. Our finding is in
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moderate
nuclear immunoreactivity of hetero-geneous
pattern (++). Eighteen out of 28 pro-static
adenocarcinomas (64.2%) showed mo-derate (++)
to strong (+++) heterogeneous nu-clear positivity
for p53 (Fig. 9). The four biopsies of TCC
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DISCUSSION
The
p53 gene product is a tumor suppres-sor
in that it restricts abnormal growth in
normal cells. It plays an important role
in transcription, in cell cycle control
and in many other aspects of growth regulation.
Mutations of the p53 gene are the most common
genetic abnormality observed in human tumors6.
In
the present study, p53 immunoreactivity
was not detected in any of the BPH cases.
A agreement with De Miguel et al. who reported
similar results and concluded that the expression
of EGFr in basal cells of BPH extended to
wider areas and that some stromal cells
appeared weakly labeled13.
In
the current study, EGFr was diffuse-moderate
in the majority of secretory cells of high-grade
PIN and in most of the cells of prostatic
carcinomas. This is similar to the findings
of Myers et al.11 and Leav et al.14 who
concluded that although most malignant cells
were positive for EGFr, the level of staining
was less than that observed in cells forming
normal or hyperplastic glands. However,
De Miguel et al. reported that in prostatic
carcinoma, both basal and columnar cells
appeared stained and the number of immunolabeled
stromal cells was higher than in BPH13.
Myers
and Grizzle suggested that the basal cell
layer represents the stem cell of the epithelium.
The strong expression of EGFr suggests that
the growth of the basal cells is regulated
by autocrine/paracrine factors. The luminal
cells express secretory products including
growth factor and proto-oncogene. They added
that these observations were consistent
with the theory that the luminal cell population
is derived from the diferentiation of the
basal cells15. De Miguel et al. were of
the opinion that EGFr acts as an autocrine
growth factor for the basal cells of the
prostatic epithelium. In BPH this action
is maintained and, in addition, the columnar
cells start to secrete EGF which is bounded
by the basal cell receptor giving rise to
a paracrine regula-tion which probably overstimulates
basal cell proliferation. In prostatic carcinoma,
besides these regulatory mechanisms, the
acquisition of EGFr by the secretory cells
develops an autocrine regulation which might
induce their proliferation13.
In
conclusion, the extent of mutated p53 protein
could be considered a prognostic tumor marker
whose abnormal expression is asso-ciated
with highly malignant prostate cancer and
may contribute to cancer progression. On
the other hand, EGFr expression is an independent
marker for the progression of prostatic
carcinoma. Further studies are needed to
evaluate the function and prognostic value
of oncogen expression in BPH and in the
pre-neoplastic and neoplastic prostate.
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Hausseler O, Epstein JI, Amin MB, Heitz
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12.
Cohen DW, Simak R, Fair WR, Melamed J, Scher
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J Urol 1994, 152:2120-2124.
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De Miguel P, Royuela R, Bathencourt R, Ruiz
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Cytokine 1999, 11:722-727.
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15.
Myers RB, Grizzle WE. Changes in biomarker
expression in the development of prostatic
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72:86-95.
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