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diagnosis of IPA induced bronchitis was assumed based on morphology
and clinical information.
Conclusion:
IPA bronchoscopy findings are non-specific and the differ-
ential diagnosis includes airway trauma, infections and neoplastic dis-
eases. Histologically, direct iron-pill damage is characterized by crystal-
line, fibrillary, golden-brown iron deposits in necrotic epithelium which
can also be identified in bronchial brushings or aspirates. Albeit rare, IPA
has potential severe complications such as haemoptysis and bronchial
stenosis. This entity should be considered in patients with risk of aspira-
tion, even in absence of a foreign body or a history of aspiration.
OFP-12-014
KI67 index in malignant epithelioid mesothelioma
T. Labiano
*
, I. Fernández, L. Nova, D. Requena, B. Aguiar, M. Alfonso,
B. Hernandez, I. Amat
*
Complejo Hospitalario Navarra, Pathology, Pamplona, Spain
Objective:
Malignant mesothelioma is an aggressive, asbestos-related
cancer with poor prognosis. Recently ki67 has been reported as an inde-
pendent prognostic marker in malignant pleural mesothelioma or perito-
neal epithelioid mesothelioma. This study examines retrospectively Ki67
in 39 consecutive malignant epithelioid mesothelioma (MEM) in order to
evaluate the prognostic significance of this marker.
Method:
Specimens from 31 consecutive MEM patients were assessed for
Ki67 expression by immunohistochemistry. We used CONFIRM anti-Ki67
(Clone 30-9) rabbit monoclonal antibody on Ventana Benchmark platform.
A pathologist scored Ki67 expression in the hottest spot and classified
samples into 2 groups on the basis of expression (<25 % = low expression
18 cases (58.1 %); and
≥
25 % = high expression in 13 cases (41.9 %)).
Eight doubtful cases were scored by ImmunoRatio - JPEG2000 Virtual
Slide microscope. Statistical analysis was assessed by SPSS 20.0.
Results:
Median patient age was 66 years, 64.5 % were male patients.
Tumour location was 87.1 % pleural and 12.9 % peritoneal. The median
percentage of Ki67-positive tumour cells was 20 % (range: 1-80 %).
There was no significant difference in the distribution with regard to
age, gender, location or histology. Survival by Ki67 index were not sta-
tistical significance for low expression vs. high expression (mean 28.89
vs. 16.62 months) (Kaplan-Meier LogRank
p
= 0.604). Mean survivals
by gender and were similar (male 22.4 vs female 26.18 months).
Conclusion:
Ki67 evaluation is difficult and may not help to predict
prognosis in MEM patients. Further studies are needed.
OFP-12-015
Incidence of therapeutic targets PD-L1 and EGFR1 in epithelial neo-
plasias of the thymus
G. Méhes
*
, L. Beke, J. Bedekovics
*
University of Debrecen, Dept. of Pathology, Hungary
Objective:
Objective:Targeted therapy of thymic epithelial tumours
(TETs) following surgery can be considered in locally aggressive or met-
astatic tumours. Our aim was to evaluate PD-L1 expression and relevant
mutations of the EGFR pathway in thymic epithelial tumours.
Method:
Materials and methods: 37 TETs (29 thymomas and 8 thymic
carcinomas) from a 10 years interval were analyzed by PD-L1 (clone
SP142, Roche) and EGFR1 by immunohistochemistry. Further, EGFR1
exon 19 and 21, KRAS exon 2, BRAF exon 15 mutation status was
determined following DNA direct sequencing.
Results:
Results: Evaluation of PD-L1 expression in tumour cell showed
a good reproducibility (inter-rater agreement, kappa-value: 0.840;
Spearman
r
= 0.966,
p
< 0.0001). In 75 % of thymic carcinomas (6/8)
and 68.96 % of thymomas (20/29) more than 1 % of tumour cells showed
PD-L1 expression. The percentage of PD-L1 positivity was statistically
not different (mean 21.87 vs. 39.82, respectively)(
p
= 0.5018). EGFR
protein expression was frequent (6/8), while none of the EGFR, KRAS
and BRAF mutations could be detected.
Conclusion:
Conclusions: PD-L1 and EGFR expression is common at
variable levels in TETs suggesting a potential benefit of targeted treat-
ments including the novel anti-PD-1/PD-L1 approach in aggressive cases.
PD-L1 evaluation criteria can be applied in thymic epithelial tumours.
OFP-13-001
EGFR T790M detection in plasma: Results from the Belgian ring
trial
K. Jacobs
*
*
AZ St. Lucas Hospital, Dept. of Clinical Laboratory, Gent, Belgium
Objective:
Half of EGFR-mutated lung cancer patients treated with anti-
EGFR TKI develop EGFR T790M-mediated resistance, resulting in dis-
ease progression. The availability of T790M targeting TKI and the pos-
sible unfeasibility of repeated biopsy testing indicate the need for sensi-
tive T790M detection in plasma.
Method:
No clinical samples were used due to ethical reasons. All sam-
ples were generated using cell line-derived sheared DNA, qualified by
digital droplet PCR in quadruple. Based on current literature, we first
defined the variant frequency and copy number range we aimed to test.
Nine samples containing each 2 ml of spiked plasma were dispatched to
the participating labs, making a total of eighty one samples.
Results:
Three participants used the Cobas EGFR workflow, five used a
digital droplet PCR (ddPCR) platform and one used a lab-developed NGS
test. The first appears robust and reproducible to the 1 % level. The lab-
developed NGS test was not able to detect the T790Mmutation at the 1 %
level and even 5 % level. The different ddPCR workflows showed dif-
ferent performances with two participants able to detect at the 0.05 %
level. However, one ddPCR user also reported a 0.05 % L858R clone as
T790M positive.
Conclusion:
The Cobas workflow appears to have the advantage of being
easy to use and interpret. But this assay is expensive per sample. The
ddPCR workflows seems to have great potential but the challenging in-
terpretation appears to be the major hurdle. The NGS test might have the
advantage of being a comprehensive analysis but seems technically the
most challenging for adequate implementation in the clinical lab.
OFP-13-002
Novel biomarker signature predicts sensitivity to PP2A activators in
triple negative breast cancer
S. Baldacchino
*
, C. Saliba, C. Scerri, G. Grech
*
University of Malta, Dept. of Pathology, Msida, Malta
Objective:
Triple negative breast cancer (TNBC) patients derive little
benefit from target-specific therapies due to lack of favourable prognostic
targets. The aim of this project was to define biomarkers to measure PP2A
complex deregulation in breast cancer, predicting a novel therapeutic
class.
Method:
Candidate PP2A activity biomarkers (PABs) were derived from
in silico analysis of RNASeqV2 data from a breast cancer cohort
(
n
= 982), retrieved from The Cancer Genome Atlas. PABs were validated
in breast cancer cellular models. The Quantigene multiplex RNA assay
was used to measure expression of these markers in a cohort of laser
microdissected breast cancer (
N
= 97) and normal breast tissue (
N
= 30).
Results:
Overexpression of these biomarkers predicts sensitivity to PP2A
activator, FTY720, and are downregulated in a dose-dependent manner.
PABs showed a lower expression in normal breast tissue compared to
Wednesday, 6 September 2017, 14:00
–
16:00, Elicium 1
OFP-13 Molecular Pathology
Virchows Arch
(
2017
)
471
(
Suppl 1
):
S1
–
S352
S39