PROGRAMME AND ABSTRACT BOOK … - page 38

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PROGRAMME AND ABSTRACT BOOK
ABS TRAC T BOOK
cytokine IL-8 and chemokine CXCL-1 are produced by cancer-as-
sociated fibroblasts from squamous cell carcinoma andmarkedly
influence the phenotype of epithelial cells. These insights into
cellular communication mechanisms may serve as developing
resource for a perspective to help taming malignancy.
References
1.
Dvořánková, et al. Histochem. Cell Biol. 2012; 137: 679–685.
2.
Kodet, et al. Tumor Biology 2013; 34: 3345–3355.
3.
Kolář, et al. Biol. Cell 2012; 104: 738–751.
4.
Plzák, et al. Anticancer Res. 2010; 30: 455–462.
Detection of ALK gene rearrangement and ALK
protein expression in the NSCLC biopsies
Plank L.
Department of Pathology, Comenius University, Jessenius
Medical Faculty and University Hospital in Martin and
Martin´s Biopsy Center, Ltd.
Introduction:
Detection of
ALK
gene rearrangement in
EGFR non-mutated non-small cell carcinoma (NSCLC) becomes
recently a part of a modern lung carcinoma biopsy diagnosis. It
represents an important approach to predict the therapeutical
response of the appropriatelly indicated ALK-targeted therapy
of NSCLC patients. This rearrangement is a very complex and
variable genetical change encoding a cytoplasmic chimeric
ALK protein with a constitutive ALK tyrosine-kinase activity.
In this study we have compared the immunohistochemical
detection (IHC) of ALK protein with the results of FISH detection
of
ALK
gene rearrangement analyzing the biopsies of patients
with EGFR non-mutated NSCLC.
Material and methods:
Analysis of
a)
ALK
gene rearran-
gement in 329 consecutive biopsies of EGFR non-mutated
NSCLC by FISH analysis using first break apart probe from either
Zytovision [ZytoLight
®
SPEC ALK Dual Color Break Apart Probe]
or Abbott/Vysis [The Vysis ALK Break Apart FISH Probe Kit (CE
Analytical)]. All the positive cases were retested by FISH analy-
sis using Zytovision fusion probe [ZytoLight
®
SPEC ALK/EML4
TriCheck™ Probe], and
b)
of ALK protein expression using ALK
Ventana automated IHC in 166 consecutive cases, all these cases
were examined also by FISH. All the evaluation approaches and
used cut-off values followed the instructions of the producers.
Results:
a)
ALK
gene rearrangement was detected in 12,5%
(41) of the 329 cases, 85% (281) of them represented „FISH
negative“ cases and approx. 2.5% (7) of the cases were not
evaluated (mostly due to a weak signal intensity). In 37 of 41
positive cases, the rearrangement was confirmed also by ALK/
EML4 fusion probe, in the remaining 4 cases the tissue was not
sufficient for the retesting. b) The concordance between the
FISH and IHC testing was 96.4%, in 6 (3.6%) of 166 cases tested
the results were discordant.
Conclusion:
The relativelly high proportion of ALK positive
cases in our series might be associated with the applied selec-
tion of the cases using diagnostic histology and IHC analyses
(selecting only adenocarcinoma and NSCLC NOS types) and
subsequent EGFR testing. The automated IHC ALK testing mig-
ht be used as a screening method for the presence of the
ALK
gene rearrangement in EGFR non-mutated NSCLC. However,
because a small number of the cases might be missed by using
IHC analysis only, we prefer to continue with a dual IHC and
FISH testing of the NSCLC cases.
Supported by grant of Ministery of Health of the Slovak
Republic Nr. 2012/24-UKMA-1 as well as by projects MBRKM and
BioMed Martin (ITMS code 26220220113, resp. 26220220187),
which are co-financed from the EU sources.
Pathology – science for patients
Ryška A.
The Fingerland Department of Pathology, Medical
Faculty, Charles University, Hradec Králové
Since the 19th century is pathology considered one of
the crucial medical sciences. Unlike in the past, when the
discipline was focused mainly on autopsies, since the last 50
years is the major part of the workload represented by surgical
pathology, where the result of the pathological examination
directly decides about the choice of appropriate treatment of
living patients.
Recent development in pathology illustrates very well how
quickly and progressively does change the current concept of
modern medicine. Whereas in the last decades of 20th century
was pathology virtually synonymous to sole morphological
examination when microscopy (including all special tech-
niques, such as electron microscopy, enzyme histochemistry
and immunohistochemistry) played the most important role
in establishing diagnosis in pathology, the start of new century
is characterized by change of paradigm. Result of modern his-
topathological examination represents a synthesis of several
tests – morphology (which still remains and for a long time
yet will remain an important and irreplaceable part of the dis-
cipline) is nowadays supplemented by methods of molecular
genetics (in situ hybridization, PCR, sequencing, CGH, etc.).
Hence, the term molecular pathology seems to be the most
appropriate designation of the discipline.
This development is mirroring the change of the clinical
practice in many fields, probably most evident in oncology.
As the oncologist today does not need for the decision about
the choice of appropriate treatment only correct histological
diagnosis (including grade, stage, evaluation of resection mar-
gins, etc.) but also much more detailed information about the
molecular profile of the neoplasm, pathologist has to detect
various prognostic and predictive markers (e.g. expression of
hormonal receptors, proliferative activity, status of HER2 in
breast carcinoma, or activating mutations of KRAS, NRAS and
BRAF in metastatic colorectal carcinoma) and include these
results in his final report.
The number of various molecular markers required to be de-
tected by pathologists is increasing very quickly and perhaps in
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