A. Pecile

A.M. Luciano

B. Banco

C. Giudice

D. Groppetti

L. Terzaghi

P.C. Dall&#8217

S.C. Modina

V. Grieco

V. Lodde

AIR Universita degli studi di Milano

SARCOGLYCAN COMPLEX IN HUMAN TRACHEAL 
TISSUE: AN IMMUNOFLUORESCENCE STUDY
G. Rizzo, G.G. Panté, G. Vermiglio, E. Filippini, A. Migliorato,
G. Santoro
Department of Biomedical, Dental Sciences and
Morphofunctional Imaging, University of Messina, Italy
E-mail: graziagiuliapante@gmail.com
The sarcoglycan complex (SGC) in made up by transmembrane
glycoproteins, α-, β-, γ-, δ-sarcoglicans, and as a part, by dys-
trophin-glycoprotein complex (DGC). The DGC also includes
dystrophin, dystroglycan (α- and β-) and syntrophins; the inter-
action of the DGC with components of the extracellular matrix
may have an important role in force transmission and sarcolem-
ma protection. Moreover, α-dystroglycan appears to have a core
protein consisting of two roughly globular domains connected
by a segment, which most likely corresponds to a mucin-like cen-
tral region.1 Several studies also demonstrated that sarcogly-
cans, which are involved in stabilization of sarcolemma during
muscle contraction, are expressed in some epithelial tissues as
gingival, breast and prostatic one.2 The aim of our study is to
demonstrate the expression of sarcoglycans in tracheobronchial
epithelial tissue, related with the presence of mucins. Mucins,
which are a superfamily of highly glycosylated proteins, are the
main constituent of mucus. In the conducting airways mucus is
produced by the tracheobronchial glands and it plays a key role
in maintaining the health of epithelial tissues. Biochemical stud-
ies shows that human tracheobronchial gland mucous (HTMG)
cells secreted typical airway mucins, and immunohistochemical
studies showed that these cells expressed  different isoforms of
MUC, especially those of our interest: MUC4 and MUC16.3 We
performed an immunofluorescence reaction, using antibodies
against β-sarcoglycan and against MUC4. To avoid any possible
fluorescence interference between the primary antibody and the
mucus gel the sample was pre-treated following a mucolytic pro-
tocol (N-acetylcystein 10% in Phosphate buffer 0.2 M).  
References
1. Bozzi, et al. BMC Biochem 2013;14:15-21. 
2. Anastasi, et al. Ital J Anat Embryol  2010;115:19-24.
3. Finkbeiner, et al. Am J Physiol Lung Cell Mol Physiol 2011;301:
L402-14.
MESENCHYMAL STEM CELLS IN HIDRADENITIS SUP-
PURATIVA: A NEW PIECE OF THE DISEASE MOSAIC 
G. Sorgentoni1, G. Lucarini1, M. Mattioli Belmonte Cima1, 
R. Di Primio1, M. Orciani1
1Department of Clinical and Molecular Sciences, Polytechnic
University of Marche, Ancona, Italy
E-mail: m.orciani@univpm.it
Hidradenitis suppurativa (HS) is a chronic inflammatory skin
disease. It generally involves the apocrine gland-bearing area of
the body and induces deep painful lesions, often associated with
other physical and psychosocial comorbidities. Onset of HS is
caused by an early occlusion of follicle, followed by dilatation of
pilosebaceous unit, rupture and release of follicular contents
into the dermis. Then, an inflammatory state is established, as
demonstrated by the various immunological abnormalities found
in skin lesions. Mesenchymal stem cells (MSCs) were success-
fully isolated from different tissues, included skin. Researches
support the hypothesis of their early involvement in various skin
diseases, such as psoriasis and atopic dermatitis. However, the
role of MSCs in HS has never been evaluated. In this study,
MSCs were isolated from lesions of patients affected by HS
(HS-MSCs) and characterized. Their immunological profile was
examined by assessing the levels of twelve cytokines related to
Th1, Th2 and Th17 pathways on conditioned medium by ELISA
array. Inflammatory activity of HS-MSCs was also studied by
immunocytochemistry. MSCs isolated from healthy subjects
were used as controls. HS-MSCs revealed an over-expression of
most of the molecules analyzed, demonstrating the activation of
MSCs in the disease towards a pro-inflammatory state. Even
more, the fact that these same cytokines play a role in HS, as
demonstrated by previous studies, strengthens the hypothesis of
MSCs contribution in disease onset and progression. 
References
Kelly G, et al. Int J Dermatol 2014;53:1186-96.
Orciani M, et al. Br J Dermatol 2017;176:1569-76.
Campanati A, et al. Arch Dermatol Res 2014;306:915-20.
PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1
(PGRMC1) EXPRESSION IN CANINE MAMMARY
TUMORS
L. Terzaghi1, B. Banco2, D. Groppetti2, S.C. Modina1, 
P.C. Dall’Acqua3, C. Giudice2, A. Pecile2, V. Grieco2, 
A.M. Luciano, V. Lodde1
1Department of Health, Animal Science and Food Safety
University of Milan, Italy; 2Department of Veterinary Medicine,
University of Milan, University of Milan, Italy; 3School of
Agricultural and Veterinarian Sciences, Sao Paulo State
University (Unesp), Jaboticabal, Brazil.
E-mail: valentina.lodde@unimi.it
Canine mammary tumors (CMT) are the most common neo-
plasms in female dogs and histopathological examination is the
gold standard for their diagnosis and classification.1 Recently,
PGRMC1 has been considered a putative biomarker for diagno-
sis and prognosis in human breast cancer, which shares some
common features with canine counterpart.2 This study repre-
sents the first description of PGRMC1 expression in CMT.
First, we evaluated PGRMC1 expression by immunohistochem-
istry in three major histopathological types: normal/hyperplas-
tic tissue, simple adenomas and simple adenocarcinomas.
Epithelial cells showed positivity to PGRMC1 and we applied a
scoring system considering the percentage of positive cells and
the intensity of expression defined as A (weak), B (moderate)
and C (strong). Normal/hyperplastic sample showed almost
100% of positive cells and a strong intensity of PGRMC1
expression. The same features were present in adenomas but
with a more variable intensity. In adenocarcinomas, the percent-
age of positive cells was lower (30-60%) and the intensity was
weak in tubular parts, while both features became progressively
negative in the solid parts of the tumor. Western blot analysis in
healthy and neoplastic mammary tissue biopsies of dogs under-
going surgery revealed the presence of the 25 kD PGRMC1
band in both types of tissue. Further investigations are in
progress to determine differences in protein level according to
the 3 different major types of tumors. Moreover, PGRMC1 will
be assessed in blood samples of dogs affected by different types
11
European Journal of Histochemistry 2017; vol. 61; supplement 2
2017_SUPPL_2_con indice.qxp_Hrev_master  01/09/17  11:58  Pagina 11
of CMT to evaluate if it could represent a prognostic serum bio-
marker as previously demonstrated in human lung and kidney
cancer.3
References 
1. Goldschmidt M, et al. Vet Pathol 2011;48:117-31
2. Ahmed IS, et al. J Pharmacol Exp Ther 2010;333:564-73.
3. Mir SU, et al. Int J Cancer 2012;131:1-9
CONTRIBUTION OF miR-145-5p/Ago2 COMPLEX TO THE
REGULATION OF EPITHELIAL-MESENCHYMAL 
TRANSITION
C. Tito1, T. Bellissimo1, S. Masciarelli1, F. Ganci2, V. Sorrentino3,
M. Cirenza3, N. Porta3, G. Cavallaro5, A. Calogero4, 
G. Fontemaggi2, V. Petrozza3,4, G. Blandino2, F. Fazi1
1Department of Anatomical, Histological, Forensic &
Orthopedic Sciences, Section of Histology & Medical
Embryology, Sapienza University of Rome; 2Oncogenomic and
Epigenetic Unit, “Regina Elena” National Cancer Institute,
Rome; 3Pathology Unit, ICOT, Latina; 4Department of Medico-
Surgical Sciences and Biotechnologies, Sapienza University of
Rome, Latina; 5Department of Surgery P. Valdoni, Sapienza
University of Rome, Italy.
E-mail: francesco.fazi@uniroma1.it
The epithelial-mesenchymal transition (EMT) is essential for
cell fate determination during development but it is involved in
pathological processes like cancer as well, being one of the first
steps in the mechanisms leading to metastasis. miR-145-5p is
one of the most widely recognized tumor-suppressor miRNAs,
able to regulate cell migration and EMT through the contribu-
tion of the RISC complex in which Argonaute (Ago) proteins
are required for target recognition and gene silencing.1 Ago2 is
an important member of the Ago family and its overexpression
correlates with a transformed phenotype in breast cancer cells.2
With the aim to unravel miR-145-5p/Ago2 contribution to the
suppression of cancer progression in epithelial tumors, here we
show that: i) miR-145-5p and Ago2 are down-regulated in
breast tumor vs normal tissues; ii) the restored expression of
miR-145-5p in breast cancer cell lines results in the reduction
of tumor phenotype; iii) Ago2 expression is positively and
specifically regulated by miR-145-5p; iv) miR-145-5p-depen-
dent Ago2 induction is necessary for the inhibition of cell migra-
tion; v) when Ago2 is depleted, the formation of an alternative
miR-145-5p/Ago1 active complex redirects miR-145-5p tumor
suppressor function and correlates with a more invasive pheno-
type in breast cancer cells. These results open to the identifica-
tion of miR-145-5p/Ago2-dependent molecular networks
involved in the maintenance and progression of cancer pheno-
type.
References
1. Bellissimo T, et al. Mol Cancer 2017;16:88.
2. Meister G. Nat Rev Genet 2013;14:447-59.
SARCOGLYCAN SUB-COMPLEX IN CARDIAC MUSCLE
OF PATIENTS DECEASED FOR SEPSI
E. Ventura Spagnolo, C. Mondello, D. Sapienza, A. Favaloro, 
D. Di Mauro, E. Filippini, C. Spoto, C. Previti, P. Gualniera, 
A. Asmundo
Department of Biomedical, Dental Sciences and
Morphofunctional Imaging, University of Messina, Italy
E-mail: elenafilippini5@gmail.com
The sarcoglycan sub-complex (SGC), member of the DGC, is
made up of six subunits of transmembrane glycoproteins named
α-, β-, γ-, δ-, ε-, and ζ-sarcoglycan (SG). This complex is local-
ized in the sarcolemma of skeletal muscle fibers and its function
is to connect the extracellular matrix to the cytoskeleton playing
a key role in stabilizing muscles and their sarcolemma during
contraction and relaxation. Clinical studies have shown that
myocardial contractility is reduced in severe sepsis which is a
life-threatening organ dysfunction which prevalence has
increased significantly in recent decades. It has been shown that
in 40% of patients with sepsis and cardiac dysfunction the
range of mortality is of 70-90% if compared to the 20% mor-
tality in septic patients without cardiovascular involvement.
Recent studies support that an increased plasma membrane per-
meability in cardiac fibers, could be responsible for sepsis-
induced myocardial dysfunction; they have also shown a
decreased expression of some DGC proteins, suggesting a role of
DGC in the pathogenesis of sepsis induced cardiomiophaty. The
critical importance of the SGC in maintaining sarcolemmal sta-
bility led us to hypothesize that even these proteins could be
involved in sepsi-induced cardiomyopathy. The aim of the present
work was to analyze the expression of sarcoglycans in human
cardiac muscle samples from deceased patients because of sep-
sis, with cardiovascular involvement. By histological and
immunofluorescence techniques we obtained results which show
critical structural alteration of cardiac fibers sarcolemma and
that the expression of β-, γ- and ε-sarcoglycans, but not the α-
sarcoglycans, is reduced. We hypothesize that members of the
sarcoglycans sub-complex could be involved in structural alter-
ation of sarcolemma, leading to sepsis induced cardiomiophaty,
even if the pathogenetic mechanism are still unclear. 
References
Celes MRN, et al. Lab Invest 2010;90:531-42.
Anastasi G, et al. Eur J Histochem 2007;51(Suppl 1):29-33.
Hunter JD, Doddi M. Br J Anaesth 2010;104:3-11.
12
37th National Congress of the Italian Society of Histochemistry, Taormina, September 22-23, 2017
2017_SUPPL_2_con indice.qxp_Hrev_master  01/09/17  11:58  Pagina 12


Progesterone receptor membrane component 1 (PGRMC1) expression in canine mammary tumors

https://air.unimi.it/retrieve/handle/2434/550256/1022413/2844_17935_1_PB_Terzaghi_EtAlii_PROGESTERONE_RECEPTOR.pdf

Progesterone receptor membrane component 1 (PGRMC1) expression in canine mammary tumors

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