Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors.
BACKGROUND
The aim of our study was to determine the integrity of the cell-cell adhesion E-cadherin-beta-catenin complex in neuroendocrine lung tumors (NELTs) and the possible involvement of Snail in its deregulation.


METHODS
The studied series consisted of formalin-fixed-paraffin-embedded tissue samples from 70 patients diagnosed with NELT (2000-2006) including tumors of low malignancy potential (3 tumorlets, 33 typical carcinoids), intermediate malignancy potential (3 atypical carcinoids) and tumors of high malignancy potential (10 large cell neuroendocrine carcinomas-LCNEC and 21 small cell carcinoma-SCLC). E-cadherin, beta-catenin and Snail expression were immunohistochemically evaluated and mRNA levels were assessed by Q-RT-PCR for E-cadherin and Snail.


RESULTS
Nuclear Snail signal was high in 46% tumors with the strongest level observed in high malignancy tumors. Furthermore, Snail levels correlated with tumor size, lymph node involvement and tobacco consumption. E-cadherin expression was downregulated in 24% cases and it was absent from the membrane in 31%, all of them cases of high malignancy potential. High E-cadherin levels and a membrane pattern were associated with tumor-free lymph node patients and inversely proportional to Snail protein expression. beta-catenin levels were weak in 43% and absent from the membrane in 59% cases. Interestingly, among high malignancy potential tumors, beta-catenin levels were significantly higher in LCNEC than in SCLC. The integrity of the E-cadherin-beta-catenin complex was retained in 37% cases, most of them carcinoid tumors, and correlated with low Snail levels, low malignancy potential and free lymph nodes.


CONCLUSIONS
Snail nuclear expression and loss of integrity of cell adhesion complex E-cadherin/beta-catenin parallels higher malignancy potential in NELTs.
Galván
J A
JA
Laboratorio del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Obra Social CajAstur, 33006 Oviedo, Asturias, Spain.
González
M V
MV
Crespo
G
G
Folgueras
M V
MV
Astudillo
A
A
D021581:Active Transport, Cell Nucleus; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012907:Smoking; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin