Sabato 27 ottobre 2012 - Pacini Editore

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H-score value of MSH2 in glandular and stromal components
were higher than other MMR system proteins. Furthermore,
MMR system protein expression correlate positively with Ki-
67 expression, but those correlations were significant only for
MSH6 and PMS2 in glandular component of ETs and MSH2 in
glandular and stromal components of ETs (p < 0.05). We found
significant differences in the whole population of our TMA
model among stromal and glandular MLH1 staining, stromal and
glandular MSH2 staining and stromal PMS2 staining.
In endometriotic tissue expressing positive glandular cytoplasmic
staining for aurora A kinase, we found differences in MLH1 and
PMS2 glandular component staining values and MSH2 stromal
and glandular component staining values. MSH2 glandular and
stromal staining values were significantly higher in ETs than
proliferative and secretory endometrium.
Discussion. Genetic instability, which leads to an accumulation
of various genetic abnormalities, has been considered an essential
component of the human neoplastic transformation process. MSI
is now considered as one of the most promising markers and
indicators of prognosis in human carcinogenesis. In premalignant
conditions in the endometrium it was found increased MSI in
atypical endometrial hyperplasia associated with endometrial
carcinoma (Ali-Fehmi et al., 2006). In this study we found no
significant microsatellite instability in endometriotic tissues.
Moreover, we found MSH2 to be significantly correlated to Ki-67
expression in both stromal and glandular components of ET and
to be expressed at a significant higher level in ET than eutopic
endometrium.
In our previous publication we found in a sub-group of women
affected by endometriosis a high cytoplasmic expression of AAK
and this group was found to be associated with higher recurrence
rate than the group with AAK negative staining ET (Calcagno et
al., 2011). In malignant pathologies high AAK expression was associated
with genomic instability (Calcagno et al., 2011), and for
this reason we analyzed MMR protein expression specifically in
this subgroup of patients where we found glandular and stromal
staining of MSH2 and glandular staining of MLH1 and PMS2
to be expressed at a higher level than healthy endometrium. The
exact role of MMR protein elevation in tumorigenesis is still
speculative but may involve aberrant and improper binding to
inactivate the MMR system. MMR protein elevation may be a
predictor of biochemical recurrence after surgery for endometriotic
lesion. This finding may identify a potential new marker for
recurrent endometriosis and uncover a potentially novel pathway
for targeted therapeutics.
During the development and progression of endometriotic lesions,
excess fibrosis may lead to scarring, chronic pain, and
alteration of tissue function, all of which are characteristics of
this disease (Nasu et al., 2009). One of the molecular changes
associated with exposure to oxidative stress is genetic damage,
including mutations to DNA single base pairs. Immunohistochemical
staining revealed an increased expression of MSH2
in tissues affected by Crohn’s disease as well in myofibroblasts
isolated from chronically inflamed bowel, which is linked to an
increased proliferative capacity of myofibroblasts compared with
control cells. In our analysis we demonstrated that MSH2 H-score
values in glandular and stromal components were higher than
other MMR proteins in ETs. Glandular MSH2 H-score values
were also higher in non-ovarian and bowel ETs than other locations
and normal endometrium; while the stromal H-score was
apparently higher in bowel ETs than all other localizations and
normal endometrium. Floer et al demonstrated in Crohn’s disease
an isolated increased expression of MSH2 in response to oxidative
stress and the increased expression of MSH2 was associated
to increased cell proliferation (Floer et al., 2008). In our study
we found MSH2 positivity to be significantly correlated to Ki-67
positivity in both stromal and glandular components. Therefore
MSH2 could play an important role in regulating ETs prolifera-
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
tion. Floer et al demonstrated in vitro that simvastatin reduced
MSH2 expression, mesenchymal cells proliferation, and intracellular
super-oxide generation (Floer et al., 2008). Recent studies
have shown that statins reduce the growth of human endometrial
and endometriotic stromal cells (Sokalska et al., 2010; Nasu et
al., 2009).
Conclusions. We found no significant microsatellite instability
in ET. The group of ETs with glandular cytoplasmic staining
for AAK had higher MMR proteins expression suggesting an
increased activity of this system in this subset of endometriotic
lesions. Furthermore, increased expression of MSH2 in endometriotic
cells appears to be linked to their increased proliferative
capacity and may be a pathophysiological mechanism underlying
endometriosis proliferation and scar formation in endometriosis.
This could be a possible therapeutic target since in recent studies
MSH2 was downregulated in vitro by statins administration.
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Expression and prognostic significance of APE1/
ref1 and nPM1 proteins in ovarian serous cancer
M. Orsaria * , A.P. Londero * , G. Tell, S. Marzinotto, V. Capodicasa,
M. Poletto, C. Vascotto, C. Sacco, L. Mariuzzi; * These
authors contributed equally to the article
University Hospital of Udine
Introduction. Ovarian cancer is a low prevalence tumor (3.1%
of female cancers in our region) but it is a leading cause of death
among gynecologic malignancies due to the advance stage at
diagnosis, recurrences, and chemoresistance. Therefore, three
points appear of paramount importance: early diagnosis (Rossi et
al., 2011), better prognosis determination (among the majority of
affected women), and therapy improvement (new possible therapeutic
targets, new drugs to overcome tumor chemoresistance,