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The Interaction of Mutant B-RAF Protein and Expression of VEGF-C as Risk Factor
for Regional Lymph Node Metastasisin Papillary Thyroid Carcinoma
Dimyati Achmad, Johan S. Masjhur, Muchlis Ramli, Bethy S. Hernowo
INDONESIA
Papillary Thyroid Carcinoma (PTC)
• Is one of the least morbid solid carcinoma
• Slow growing tumor
• Favorable long-term survival
But Approximately 33% to 61% of PTC will have
involvement of cervical lymph nodes at the
time of diagnosis
The regional lymph node metastasis in PTC
appear no correlation with overall survival but
consistenly correlate with local or regional
reccurence.
Until now, molecular pathogenesis of lymph
node metastasis in PTC is still controversial.
Under this circumstances, we would like to
emphasis on the risk factor that plays an
important role in the migration and invasion of
PTC cells to extra thyroidal structure, which is
related to mutant B-RAF protein and also VEGF-C
expression in lymphangiogenesis process.
The aim of this study is to prove the existence
of interaction between mutant B-RAF protein
and VEGF-C expression, as the risk factor of
lymph node metastasis in PTC.
This study is:• Case – control study
• Comparative observation between:–38 subjects PTC with LN. metastases–38 subjects PTC without LN. metastasesas a control group, selected by matching process.
• The Independent Variable–Mutant B-RAF protein–VEGF-C expression
• The Dependent Variable–Regional lymph node metastasis
• The mutant B-RAF protein and VEGF-C expression were identified by immunohistochemistry examination.
• And the result define by histoscore: based on McCarty Criteria (1995).
Highest intensity 50 – 80% distribution
The Analysis:
We analyzed data by :• The McNemar bivariant analysis test
For compare each independent variable with dependent variable
• The double logistic regression multivariant analysis test and the stratification analysis testFor compare two independent variable with dependent variable
The Associaton Between Mutant B-RAF Protein and LN. Metastasis in PTC
The result showed an evidence significant association(p < 0.05)
Mutant B-RAF Protein
Casen = 38
Controln = 38
p. Value
Positive 32 (84.2%) 18 (47.4%)0.023
Negative 6 (15.8%) 20 (52.6%)
Mc Nemar testOR: 5.92 (95% CI: 2.01 – 17.45)
Results:
The Associaton Between VEGF-C Expression and LN. Metastasis in PTC
The result showed unrelated association(p > 0.05)
VEGF-C Expression
Casen = 38
Controln = 38 p. Value
Positive 33 (86.8%) 30 (78.9%)0.272
Negative 5 (13.2%) 8 (21.1%)
Mc Nemar testOR: 1.76 (95% CI: 0.51 – 5.97)
An Interaction Between Mutant B-RAF Protein and VEGF-C Expression as Risk Factor of LN Metastasis in PTC
The multivariant analysis testShowed: a significant resultp = 0.001, OR 5.92 (95% CI: 2.01 – 17.44)
The stratification analysis testShowed: a significant resultp = 0.004, OR 6.44 (95% CI: 1.23 – 33.80)
Summary
MAPK
MutantB-RAF Protein
PTC Cell
Conclusions :
Molecular Pathogenesis Lymph node metastesis in PTC occurs due to interaction between two processes: Invasion of PTC cell to Extrathyroidal Structure and Lymphangiogenesis process.
The interaction between mutant B-RAF protein and VEGF-C expression, has a role as a dominant risk factor of lymph node metastasis in PTC.
Thank You
Summary of Significant Differences
• Mutant B-raf• Initiation of MAPK
pathway occur through Central Protein
• Activation HIF1α occur through two mechanisms
• Hypoxia Condition and Crosstalk between ERK and HIF1α
• Shorter Process
• Non-Mutant B-raf• Initiation of MAPK
pathway occur through Thyrocinekinase receptor
• Activation HIF1α occur through hypoxia condition
• Longer Process• No crosstalk
Summary
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