mTOR Expression in Pulmonary Neuroendocrine Tumors
Paula A Toro, Cristina Alenda, Gloria Peiro, Ana Teruel, Estefania Rojas, Ignacio Aranda. Hospital General de Alicante, Alicante, Comunidad Valenciana, Spain
Background: The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth. mTOR plays a pivotal role in the proliferation and progression of several neoplasms; nevertheless, its role in neuroendocrine (NE) tumors of the lung has not been extensively evaluated. Therefore, the aim of our study was to analize the mTOR activation status in a series of neuroendocrine lung tumors (NELT).
Design: A total of 62 cases of NELT were retrieved from the Surgical Pathology files (43 typical carcinoid-TC-, 8 atypical carcinoid –AC-, 8 large cell neuroendocrine carcinomas –LCNEC-, and 3 small cell carcinomas –SCC-). After identifying tumor area for each case from formalin-fixed paraffin-embedded tissue blocks, 0.4-mm-thick cores were punched and embedded in the donor paraffin block. Tissue microarrays were stained with antibodies against phospho-mTOR (Ser2448, Cell Signaling) and Ki-67 (MIB1, Dako), as a marker of proliferation activity. mTOR tumor cell positivity (diffuse cytoplasmic) (percentage and intensity) was semi-quantitatively scored (range 0-300). Cases with score ≥10 were defined as positive. Inmunohistochemical results were correlated as well as histologic subtype. A p value < 0.05 was considered significant.
Results: Age of patients ranged from 16 to 74 (mean 52); 52% were men and 48% women. mTOR overexpresión was predominantly seen in TC and AC (84% and 87%, respectively) whereas the expression in LCNEC and SCC was lower (12% and 33%, respectively) (p < 0.000). Tumors with mTOR overexpression had lower proliferative rates, as valorated by Ki-67 (p=0.006).
Conclusions: Our findings suggest that the level of expression of mTOR is associated with better differentiated NELT and decreases with more aggressive histologic subtypes. Due to the availability of therapeutic targets that modulate this molecular pathway, these results could be relevant for the selection of patients treatments.
Supported by Grant N-03 from FICV-HGUA
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 292, Tuesday Afternoon