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Chromosome. A possible therapeutic role of AR in MBC is emerging in
the recent literature. The aim of this study is to investigate the role of the
X chromosome in MBC development.
Method:
Seventy-three consecutive MBC cases were reviewed. When pres-
ent areas of DCIS and gynecomastia surrounding the invasive carcinoma
were also studied. Cases were tested by FISH to assess the X chromosome
status and AR amplification, ICH for AR expression, and bisulfite-
Sequencing for AR DNA methylation.
Results:
X chromosome gain was observed in 74,7 % invasive MBC, in
20.6% of DCIS and in 14.6 %of gyecomastia when associated to cancer. AR
gene copy number increased parallel to the number of X chromosomes. On
ICH, AR expression (positive staining in > 1 % of the neoplastic nuclei), was
present in 96.6 % of invasive MBC tested. Absence of AR DNAmethylation
was detected for both epialleles in 9\cr10 cases.
Conclusion:
These data confirm that X chromosome gain plays a role in the
neoplastic transformation of male breast epithelial cells and is related with AR
polysomy. AR gene copies appear to be unmethylated, therefore maintaining
their function.
OFP-08-015
Axonogenesis and vascular proliferation are associated gene expres-
sion programs in hormone receptor negative breast cancer
E. Wik
*
, S. Aziz, K. Krüger, G. Knutsvik, A. Svanøe, B. Davidsen, T.
Aas, I. Stefansson, L. A. Akslen
*
University of Bergen, CCBIO, Dept. of Clinical Medicine, Norway
Objective:
Interactions between cancer cells, vasculature and nerves have
been suggested as important for tumour progress. We aimed to explore these
relations in subtypes of breast cancer (BC), with particular attention to novel
treatment targets.
Method:
We analyzed multiple BC mRNA cohorts and signatures
reflecting vascular proliferation and axonal sprouting were explored. A
cohort of primary BC tissue (
n
= 461) was studied by IHC for validation
(Factor VIII-Ki67; Neurofilament).
Results:
High angio- and axonogenesis signature scores associated with
ER/PR negativity, a basal-like phenotype and shorter survival. Notably,
the angio- and axonogenesis scores were significantly associated, and a
jointly activated neuro-angiogenic profile strongly associated with the
basal-like phenotype and gene sets reflecting hypoxia and immune re-
sponses. An association between vascular proliferation and axon density
by IHC was found. Through a drug signature database (Connectivity-
Map), compounds with dopaminergic action were identified as negatively
correlated with the expression profile of VP-high tumours.
Conclusion:
Our findings indicate vascular proliferation and
axonogenesis as coordinated programs in aggressive breast cancer.
Dopaminergic drugs are suggested as potentially relevant, especially for
the basal-like subtype with few treatment options.
OFP-09-001
Large nested variant of urothelial carcinoma in urinary bladder:
Histopathological analysis in 18 transurethral resection cases
E. Hacihasanoglu
*
, K. Behzatoglu, O. Okcu, Y. Cakir, S. Baykal Koca
*
Istanbul Training and Res. Hospital, Dept. of Pathology, Turkey
Objective:
Endophytic growth pattern in urothelial carcinomas (UC)
cause problems in evaluation of invasion, especially in low-grade cases.
Method:
Haematoxylin-eosin stained slides of bladder transurethral re-
section materials submitted to our department in 2008-2017 were re-ex-
amined. There were 18 UC cases with large nested pattern of invasion.
Results:
The mean age was 70 and 83 % were male. Mean tumour
diameter was 4,83 centimetres. Non-invasive UC component was present
in all cases; low-grade in 6, high-grade in 1, low and high-grade in 11
cases. Twelve and 6 cases were pT1 and pT2, respectively. All cases had
invasive component composing of medium-large nests. Additionally, 2
cases had focal small invasive nests and 2 cases had areas of conventional
invasive UC. Stromal-tumour interface was irregular in 16 cases, whereas
2 cases had invasive nests with rounded contours. Fibrous stromal reac-
tion and/or stromal lymphoid infiltration were present in 17 cases.
“
Budding
”
, described as small nests in stromal interface of medium-
large nests was a remarkable feature in 13 cases. Angiolymphatic inva-
sion and necrosis were detected in 2 and 5 cases, respectively.
Conclusion:
Large nested pattern of invasion in UC causes diagnostic
difficulty. Irregularity of nests, presence of stromal reaction,
“
budding
”
and muscularis propria invasion can be helpful in differential diagnosis.
OFP-09-002
Descriptive statistical analysis of mismatch repair proteins (MLH1,
MSH2, MSH6 and PMS2) immunohistochemical expression in pros-
tate cancer: Correlation with Grade Groups (ISUP/WHO 2016)
R. Albero
*
, A. Lloret, N. Juanpere, M. Iglesias, M. Lorenzo, X. Duran, L.
Fumadó, L. Cecchini, S. Hernández, J. Lloreta
*
Hospital del Mar, Dept. of Pathology, Barcelona, Spain
Objective:
The role of DNA Mismatch Repair (MMR) genes in prostate
cancer (PrCa) is poorly understood. We investigated the correlation be-
tween MMR protein expression (MLH1, MSH2, MSH6, PMS2) in PrCa
and their relationship with Grade Groups (GG).
Method:
Immunohistochemical expression of MMR proteins was
assessed. GG and Nuclear Histoscore method (NH = 0-300) were used to
group 126 PrCa cases (Parc Salut Mar-Biobank, Barcelona) in three cate-
gories: Group0, NH: 0
–
10; Group1, NH: >10
–
100; and Group2, NH: >100.
Results:
In assessable TMA cores, MSH2 expression was lost in 7/108
(6.5 %), MSH6 in 54/97 (55.7 %), MLH1 in 11/114 (9.6 %) and PMS2 in
2/114 (1.8 %). The two last results were paradoxical compared to the
general literature (lost MLH1/preserved PMS2, 7/114 cases, 6.1 %).
MSH2/MSH6 heterodimer and MLH1/PMS2 losses were detected in
6/98 (6.1 %) and in 1/113 (0.9 %) cases, respectively. MSH6 loss was
statistically associated with GG (
p
= 0.005), with most cases belonging to
GG2.
Conclusion:
This preliminary study supports the fact that MMR proteins
role is poorly defined in PrCa. Unusual patterns are probably conditioned
by tumour heterogeneity and intrinsic prostate tissue properties. These
results must be correlated with molecular analysis in order to clarify their
relationship with familial PrCa. Funding: Grants: ISC-III (PI15/00452),
Jordi-Gras 2016.
OFP-09-003
Clinicopathologic analysis of Birt-Hogg-Dube Syndrome (BHD)-as-
sociated renal cell carcinomas (RCC)
M. Furuya
*
, I. Kato, Y. Nagashima, H. Hasumi, M. Yao, M. Baba, R.
Tanaka, Y. Nakatani
*
Yokohama City University, Dept. of Molecular Pathology, Japan
Objective:
Birt-Hogg-Dube syndrome (BHD) is a newly emerging he-
reditary disorder caused by germline mutation of FLCN. Multiple renal
cell carcinomas (RCCs) determine the prognoses of BHD patients. Most
BHD-RCCs are chromophobe RCCs or hybrid oncocytic/chromophobe
tumours (HOCTs). Differential diagnosis between BHD-RCCs and spo-
radic counterparts is important because FLCNmutation carriers have high
risks of developing bilateral multiple RCCs. The aim of the study is to
find useful markers for differentiation between BHD-RCCs and
histology-matched sporadic counterparts.
Tuesday, 5 September 2017, 17:15
–
19:15, D203
OFP-09 Uropathology
Virchows Arch
(
2017
)
471
(
Suppl 1
):
S1
–
S352
S26