pERK in early stage NSCLC.

MENDIZABAL J; GALMES M; N. SPIZZAMIGLIO; MARESCO E; SACCOLINI M; PEDERNERA A; NAPOLI J; JANKILEVICH G; PONTILLO C; ZELASCHI D; HEWITT S; GUTKIND JS; MOLINOLO A; COSO OMAR

Buenos Aires

Congreso; 4th Latin American Conference on Lung Cancer.; 2010

Abstract 164 pERK in early stage NSCLC Type: Scientific Paper Abstract (for review) Topic: 2. Early Stage NSCLC (stage I-III) J.E. Mendizábal1, M.A. Galmés2, N. Spizzamiglio2, E. Mareso3, G. Jankilevich2, M. Saccolitti2, A. Pedernera4, J. Nápoli5, C. Pontillo1, D. Zelaschi1, S. Hewitt6, S. Gutkind7, A. Molinolo7, O.A. Coso1; 1IFIBYNE - FCEN - UBA - CONICET/ARGENTINA, 2Hospital Carlos G. Durand/ARGENTINA, 3Facultad de Medicina, Universidad de Moron/ARGENTINA, 4Hospital Tornú/ARGENTINA, 5Centro Gallego de Bs.As./ARGENTINA, 6Laboratory Of Pathology, CCR, NCI, NIH/UNITED STATES OF AMERICA, 7Oral and Pharyngeal Cancer Branch NIDCR - NIH/UNITED STATES OF AMERICA Background Erk1/2 (extracellular signal regulated kinases) are classical members of the MAPK (mitogen activated protein kinase) family. These serine/threonine kinases are key components of pathways that transduce extracellular signals and activate nuclear transcription factors. These events are widely associated to cell growth and require phosphorylation of the MAPK by upstream components of the signaling cascade. The presence of the resulting molecular product (phosphorylated Erk or pErk) is indicative of activation of this MAPK pathway linked to cell transformation. The molecular events leading to lung cell transformation remain largely unknown and data related to MAPK in NSCLC is still controversial. Methods Using tissue microarray technology we studied by inmunohistochemistry the expression and subcellular localization of pErk in Lung Cancer samples from Argentinean patients and correlated our data with clinicopathological variables in NSCLC. 355 lung cancer samples, collected from patients by the same surgical team from 1990 to 2004, were used to assemble the tissue array. The results of this retrospective study that includes 253 NSCLC were analyzed by x2, Fisher exact test, Kaplan Meier and Logrank tests. Results and Conclusions pErk was stained in 60,5% NSCLC (n=253), 58,6% in normal tissues (n=29) and 62,5% in normal lungs (n=8). 11,5% of T1 (n=26) have intense (+++) stain, twelve times the value in the T2T3T4, 0,91% (n=219) p=0,0092639. There were no statistically significant differences related to gender. While there were no differences in intensity stain between normal tissues and T1 samples, p=0,676, it was significantly different between normal tissue and the T2T3T4 group, p=0,00515185 (Fig2 A&B) Nuclear localization increases with stain intensity. Cases with + stain were nucleocitoplasmatic positive in 57,5% (n=120), ++ in 81,48% (n=27) , +++ in 100% (n=6) (negatives n=100) p=<0,00000001 (Fig1 B/C/D/A). Center 2 patients with nuclear stain had a minor global survival than the rest (mean 935,75 vs 1535,2 days) p=021 (Fig2 C). In summary, T1 tumors show a pErk expression pattern closer to the onepresent in normal Página 1 de 2 http://abstracts.webges.com/submission/preview/print_publication.php?publication_id... 26/03/2010 tissues than to T2 tumors. Nuclear localization seems to be highly linked to stain intensity and is absent in normal samples. Nucleocitoplasmatic stain associates with lower survival in samples from patients of a representative center. Página 2 de 2 http://abstracts.webges.com/submission/preview/print_publication.php?publication_id... 26/03/2010