SCIENTIFIC REPORT 2010 - 2011 - IOV

aNalySiS Of ThE prOGNOSTiC aND prEDiCTivE impaCT Of
EGfr aND kraS muTaTiONS, aND Of EGfr fiSh iN
aDvaNCED luNG aDENOCarCiNOma
Principal Investigator: Adolfo Favaretto
The non-small cell lung cancer (NSCLC) has demonstrated
considerable heterogeneity of biological and clinical behavior.
Reversible inhibitors of EGFR have proven effective in a group of
patients with specific clinical and molecular features. Mutations in
the tyrosine domain of EGFR were found to be the best predictor
in terms of objective response and PFS, while FISH for EGFR
seems to identify a larger group of patients who might benefit
from treatment. KRAS mutations are associated with failure to
respond to such therapy. The three molecular markers will be
analyzed retrospectively in patients with stage IIIB and IV NSCLC
undergoing surgery for diagnostic or therapeutic purposes; the
patients will be selected based on the presence of at least one of
the clinical features which appear to be predictive of response to
EGFR inhibitors (non-smoker status, female). The purpose of this
study is to determine whether mutations in the tyrosine domain
of EGFR or gene amplifications evaluated by FISH analysis can
confirm their predictive value in a selected population of patients
with clinical features indicative of response to inhibitors of EGFR
tyrosine kinases, and to assess their prognostic value in a specific
clinical context. Samples were collected from 67 patients with
lung adenocarcinoma. Mutational analysis of EGFR (exons 18-
21), KRAS (exon 2) and FISH analysis for EGFR are ongoing.
The overall survival and disease-free survival will be analyzed in
relation to the molecular findings to investigate their prognostic
significance. The influence of treatment with inhibitors of EGFR
on overall survival and disease-free survival in different patient
groups will then be analyzed.
EvaluaTiON Of CirCulaTiNG TumOr CEllS (CTC)
aND ENDOThElial prOGENiTOr CEllS (EpC) aS a
prOGNOSTiC faCTOr iN lOCally aDvaNCED luNG
CaNCEr (NSClC)
Principal Investigator: Adolfo Favaretto
Patients with locally advanced NSCLC have a median survival
of about 1 year, and at 3 years about 20% are still alive. Aim of this
study is to assess whether two cell markers could partially explain
THE DEPARTMENTS - DEPARTMENT OF CLINICAL ONCOLOGY
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this biological heterogeneity. CTC are present in many metastatic
solid tumors. Their measurement in breast cancer has a prognostic
and predictive value. EPC are cells derived from bone marrow and
may play an important proangiogenetic role in the early growth
of metastases. In 30 NSCLC patients we plan to count CTC
and EPC at the beginning and at the end of concurrent chemoradiotherapy.
In the case of sequential therapy, the count is also
planned at the end of each treatment. The CTC will be evaluated
with the CellSearch (Veridex, LLC, Warren, NJ) system.
To this end, 15 ml of peripheral blood are incubated with
magnetic nanoparticles conjugated with monoclonal antibody
to the cell surface marker EpCAM, specific for epithelial cells.
Through a magnetic field, EpCAM positive cells are selected
and labeled with antibodies specific for white blood cells (anti-
CD45) and epithelial cells (anti-cytokeratin 8, 18, 19) and a
specific marker for cell nuclei (DAPI). A CTC, by definition,
must express EpCAM, have a nucleus (DAPI positivity), and
express markers for epithelial cells but not leukocytes. EPC are
defined as endothelial cells in the peripheral blood expressing
C-kit, VEGFR2, VE-cadherin but not expressing CD11b. Up to
now, 6 patients with locally advanced NSCLC were enrolled and
completed the counting of CTC and EPC.
TumOr markErS fOr aDENOCarCiNOma Of ThE
ESOphaGuS aND CarDiaS. a rETrOSpECTivE STuDy
Principal Investigator: Vanna Chiarion-Sileni
Tumor markers may correlate with the presence or progression
of cancer. In cancers of the colon and pancreas, the predictive
and prognostic value of CEA and Ca199 are defined, whereas
for cancers of the esophagus and cardias only a few studies
have evaluated the significance of their increase in the natural
history of disease. The purpose of this study is to evaluate, both
retrospectively and prospectively in patients treated from 1998
with cardias gastric cancer, the significance and predictive value
of CEA and Ca199 and their possible prognostic and predictive
role.
Data collection began in March 2010 and will continue until
a suitable number of patients to obtain statistical significance will
be reached. In case of evidence of a predictive and/or prognostic
role, a prospective validation study will be proposed by the Italian
Research Group on Biomarkers.