Acta Dermato-Venereologica 98-10CompleteContent | Page 19
985
SHORT COMMUNICATION
Changes in Androgen Receptor Expression as a Molecular Marker of Progression from Normal
Epithelium to Invasive Cancer in Elderly Patients with Penile Squamous Cell Carcinoma
Valerio Gaetano VELLONE 1,2# , Emanuele COZZANI 3# , Leonardo PEÑUELA 5# , Roberto RUSSO 3 , Bruno SPINA 2 , Carlo TONCINI 2 ,
Carlo TERRONE 4# and Aurora PARODI 3#
Pathology, Department of Integrated Surgical and Diagnostic Sciences, University of Genoa, 2 Pathology Unit, San Martino Polyclinic Hospital,
Section of Dermatology, DISSAL, University of Genoa, San Martino Polyclinic Hospital, Via A. Pastore, 1, IT-16132, Genoa, 4 Department
of Urology, University of Genoa, IRCCS San Martino-IST, and 5 Fetal and Perinatal Pathology Unit, Istituto Giannina Gaslini, Genoa, Italy.
E-mail: [email protected]
#
These authors equally contributed to this paper.
1
3
Accepted Jul 5, 2018; Epub ahead of print Jul 6, 2018
Penile squamous cell carcinoma (SCC) is uncommon
(1, 2). Two distinct pathways lead to penile SCC: one
is linked to human papillomavirus (HPV) infection and
is associated with undifferentiated penile intraepithelial
neoplasia (PeIN); the other is linked to non-neoplastic
epithelial disorders, such as epithelial hyperplasia or li-
chen sclerosus (LS) and is associated with differentiated
PeIN (3–7). Little is known about molecular changes in
the genesis of penile cancer. Only one study has reported
the expression of hormonal receptors, such as oestrogen
receptors (ERα), and androgen receptor (AR) in normal
penile epithelium, with no sign of progesterone receptor
(PR) expression (8). Thus far, however, no studies have
investigated the possible role of these receptors in the
transition from normal epithelium to male genital LS or
penile SCC.
The aims of the present study were to describe his-
tological and immunohistochemical features of SCCs,
to examine the modulation of hormonal receptors ERα,
AR, PR and molecular proliferation markers (p53 and
Ki-67) in normal penile epithelium and in SCC, and to
extend this evaluation to penile lesions adjacent to SCC.
MATERIALS AND METHODS
This retrospective study was conducted on 21 consecutive patients
who had undergone surgical resection of penile cancer in San
Martino Polyclinic Hospital, Genoa, Italy, in the period 2006 to
2015. All the curative-intended surgical specimens (wide exci-
sional biopsies, partial and total penectomies) were fixed in 10%
buffered formalin, processed and embedded in paraffin to obtain
haematoxylin-eosin-stained slides. In each case, a representative
block containing both normal (NE) and tumour tissue (K), as well
as the SCC-associated penile lesion (PRE), was chosen in order
to obtain further sections. Squamous multi-layered epithelium
devoid of major inflammation, and displaying normally orienta-
ted cellular maturation, was considered normal epithelium (NE).
Squamous cell hyperplasia was defined as epithelial hyperplasia
and hyperkeratosis, increased mitotic figures in basal and prickle
cell layers and mild dermal chronic inflammation, with no aty-
pia. Lichen sclerosus was defined as severe hyperkeratosis, thin
epidermis and presence of a homogenized band of dense fibrosis
affecting the papillary dermis. Differentiated PeIN was defined
as hyperkeratosis, hypergranulosis, acanthosis, with cytological
atypia. SCC was defined as variable cytological atypia, high
mitotic index, infiltrating pattern and presence of keratin pearls.
The following antibodies were used for immunohistochemistry
testing: Androgen Receptor (Cell Marque, Rocklin, USA, Clone
SP107, pre-diluted), Estrogen Receptor α (Ventana, Innovation
Park Dr. Tucson, USA, Clone SP1, pre-diluted), Ki67 (Ventana,
Clone 30-9, prediluted), Progesterone Receptor (Ventana, Clone
1E2, pre-diluted), p53 (Ventana, Clone DO-7, prediluted). Appro-
priate negative and positive controls were implemented according
to the manufacturer’s data-sheets. Expression was evaluated by
considering the percentage of cells exhibiting immunoreactivity
as well as intracellular localization. In normal tissue and in SCC-
associated penile lesions, analysis was restricted to the epithelial
component, where the number of positive (brown-stained) cells
in a random field of 300 cells was counted; the reactivity pattern
of cell positivity was also recorded (i.e. basal, lower, middle and
upper thirds of the epithelium, or diffuse). In tumours, the number
of positive cells was counted in 5 separate fields of 100 cells each
(total number 500 tumour cells). The results were expressed as
the mean percentages of positively stained nuclei in relation to
the total number of epithelial- or tumour-cell nuclei considered.
The staining intensity was not evaluated.
RESULTS
Clinical-pathological features of the study population
are shown in Table SI 1 .
Immunohistochemistry
Androgen receptor. In NE, SCC-associated lesions
and SCCs, AR expression displayed mean ± standard
deviation (SD) values of 52.0 ± 32.7%, 28.1 ± 28.0%
and 0.9 ± 3.0% labelled cells, respectively. Moreover,
positivity in SCCs was confined to the lower third of the
epithelium; in SCC-associated lesions, the distribution
of positivity was variable; in NE, positivity was diffuse.
Significant differences (p < 0.001) in staining indexes
was observed between NE and K and between PRE
and K. Although the AR staining index proved lower in
PRE than in NE, the difference failed to reach statistical
significance (Fig. S1 1 ).
Oestrogen receptors α and progesterone receptor. ERα
immunoreactivity was recognized in 5 cases only, and
was very weak. None of the specimens tested showed
substantial expression of PR.
p53. In NE, SCC-associated lesions and SCCs, p53
expression displayed mean ± SD values of 2.8 ± 5.0%,
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3004
1
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2018 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3004
Acta Derm Venereol 2018; 98: 985–986