Publication in Urologic Oncology
SPINK1 expression in relation to PTEN
and ERG in matched primary and lymph node metastatic prostate cancer:
Implications for biomarker development
Abstract
Background
SPINK1,
ERG, and PTEN are proposed prognostic biomarkers in prostate cancer
(PCA). However, their relations and patterns of expression in primary
and metastatic lymph node (LN) PCAs are not fully explored.
Methods
A
tissue microarray of matched primary PCA and LN metastasis was
constructed from 36 patients. SPINK1, ERG, and PTEN expression statuses
were assessed by immunohistochemistry and correlated with each other.
Results
SPINK1
and ERG were expressed in 25% and 42.7% of primary PCA cases, respectively. PTEN loss of any degree was observed in 91.7% of primary
PCA cases, with 54.2% showing complete loss. In primary PCA, 12.5% of
the cases showed SPINK1+/ERG−phenotype, 16.7% showed
SPINK1+/ERG+phenotype, 25.0% showed SPINK1−/ERG+phenotype, and 45.8%
showed SPINK1−/ERG−phenotype. All PCAs with expression of either SPINK1
or ERG also exhibited PTEN loss, whereas PCA without PTEN loss (2 cases)
expressed neither. In primary PCA, evaluation of combined ERG and
SPINK1 status, but not SPINK1 individually, was associated with a
significant difference in proportion of Gleason patterns (P =
0.013), with the SPINK1+/ERG+and SPINK1−/ERG−phenotypes represented more
in Gleason pattern>7 PCAs. In LN metastases, the overall SPINK1
protein expression frequency was significantly lower (6.5% of cases)
compared with primary PCA (P = 0.03). Only 16.7% of cases with
positive SPINK1 expression in primary PCA maintained expression in LN
metastases. The down-regulated SPINK1 expression in LN was primarily
because of a reduction in the SPINK1+/ERG+PCA subpopulation to 3.5% of
cases (P = 0.16 compared with primary PCA). The frequencies of
ERG expression and PTEN loss were relatively stable in primary PCA and
LN metastases.
Conclusion
SPINK1
expression is dynamically regulated with up-regulation in primary sites
of nodal metastatic PCA and down-regulation in LN metastases. The
increased SPINK1 expression in primary site of nodal metastatic PCA is
secondary to an increased frequency of SPINK1+/ERG+tumors. In primary
PCAs, the SPINK1+/ERG+phenotype is associated with higher Gleason grade,
suggesting that this phenotype may mark a more aggressive PCA
subpopulation with higher risk of LN metastases.
