Annual Meeting Proceedings Part 1 - American Society of Clinical ...

TPS10634 General Poster Session (Board #54C), Mon, 1:15 PM-5:15 PM
Highly sensitive determination of PIK3CA exon 9 and 20 hotspot mutations
in breast tumors. Presenting Author: Alexandre Harle, Centre Alexis
Vautrin, Pathology and Tumor Biology Dept, EA4421 SiGReTO Nancy
University, Vandoeuvre-lès-Nancy, France
Background: Hotspot mutations in exons 9 (E542K and E545K) and 20
(H1047L and H1047R) of PIK3CA gene encoding for the p110� catalytic
subunit of Phosphatidylinositol 3-kinases (PI3K) are found in approximately
25% of breast carcinomas. PIK3CA mutations cause the overactivation
of PI3K/AKT/mTOR pathway and lead to resistance to anti-HER2
targeted therapies in breast cancers, are involved in response to anti-mTOR
agents and are proposed as molecular diagnosis marker for PI3K inhibitors.
A highly sensitive method is required to detect PIK3CA mutations in
paraffin-embedded tumor tissues. Methods: We developed a real-time PCR
assay using allele-specific scorpion primers and amplification refractory
mutation system (PCR-ARMS) to detect hotspot mutations in exons 9
(E542K and E545K) and 20 (H1047L and H1047R) of PIK3CA of PI3K.
Results: PIK3CA mutations were analyzed in 102 paraffin embedded breast
tumors (88 invasive ductal carcinomas and 14 lobular ductal carcinomas).
All specimens were validated by pathologist examination and processed for
DNA extraction and PCR. PIK3CA exon 9 and 20 mutations were found in
22.5% of the specimens, 39.1% in exon 9 (26.1% for E542K, 13.0% for
E545K) and 60.9% in exon 20 (17.4% for H1047L and 43.5% for
H1047R). These results were comparable to the literature data (�²�0.327
;p�0.05). PCR ARMS was found to be highly sensitive, able to detect 0.5
% mutated DNA. Conclusion: PCR ARMS assay is highly sensitive for
PIK3CA exon 9 and exon 20 hotspot mutations analysis in breast
carcinomas as molecular marker for anti-HER2 and PI3K inhibitors
response prediction.
Tumor Biology
689s
TPS10635 General Poster Session (Board #54D), Mon, 1:15 PM-5:15 PM
ACRIN 6684 assessment of tumor hypoxia in glioblastoma using 18Ffluoromisonidazole
with PET and MRI. Presenting Author: Elizabeth Robins
Gerstner, Massachusetts General Hospital, Boston, MA
Background: Glioblastoma (GBM) is an aggressive type of primary malignant
brain tumor and despite treatment with surgery, radiation, and temozolomide
(TMZ) chemotherapy, median overall survival (OS) remains poor. A
pathologic hallmark of GBM is tumor necrosis, a suspected result from
endogenous tumor hypoxia. Angiogenesis is stimulated by hypoxia-driven
signaling cascades and is required for tumor proliferation. The inefficient
blood supply of these hypoxic tumors also limits the efficacy of chemotherapy
and radiotherapy. Surviving hypoxic tumor cells may be selected
out and proliferate as a more aggressive tumor subtype, therefore hindering
OS. 18F-Fluoromisonidazole (FMISO) is a PET radiotracer whose uptake in
hypoxic tissues can be measured radiographically. The degree of tumor
hypoxia has been negatively associated with time to tumor progression and
survival (Spence et al, 2008). Knowledge of the degree/distribution of
tumor hypoxia by PET uptake and perfusion MRI parameters may provide
prognostic information and help guide therapy for patients with GBM.
Methods: In this phase II prospective single arm multi-institution study,
patients will undergo baseline FMISO PET and MR imaging two weeks prior
to chemoradiotherapy (CRT). A subset of patients will receive a second
FMISO PET one week prior to CRT to assess reproducibility. Clinical
outcomes of OS and 6-month progression-free survival (PFS-6) will be
correlated to PET and MRI parameters. Eligibility: Pathologically confirmed
GBM with residual tumor after surgery (including T2/FLAIR hyperintensity
consistent with tumor) scheduled to receive standard fractionated radiation
therapy and temozolomide alone or with an anti-VEGF agent or PARP
inhibitor. Current enrollment: 22 patients of 50 sample size Contact
information: Please contact the PI, Elizabeth R. Gerstner, MD
(egerstner@partners.org) for additional information. Significance: With a
better understanding of the extent of tumor hypoxia and changes in hypoxia
levels from treatment, more effective therapies could be developed to
inhibit GBM growth, target hypoxic areas and individualize patient care.
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