E-cadherin-beta-catenin adhesion complex in neuroendocrine tumors of the lung: a suggested role upon local invasion and metastasis.
Dysfunction or loss of the intercellular adhesion complex E-cadherin-beta-catenin is frequent in non-small cell lung carcinomas in which E-cadherin and beta-catenin loss has been considered to be a molecular marker of tumor progression and poor prognosis. With an aim of evaluating the expression of the E-cadherin-beta-catenin complex and its prognostic role in neuroendocrine tumors (NET) of the lung, immunohistochemical analysis was performed in 102 NET, including 16 low-grade typical carcinoids, 8 intermediate-grade atypical carcinoids, 37 large-cell neuroendocrine carcinomas (LCNEC), and 41 small-cell lung carcinomas, both high-grade tumors. Impaired E-cadherin expression (loss or cytoplasmic delocalization) was observed in 80 (78%) of 102 samples, and impaired beta-catenin expression was noted in 74 (72%) of 102 cases. The impaired expression of E-cadherin and beta-catenin was observed with a higher frequency in high-grade tumors (87% and 83%, respectively) than in carcinoids (50% and 37%, respectively; P < 0.0001). Impaired expression of the E-cadherin and beta-catenin molecules also correlated with lymph node metastasis (P = 0.0001 and P = 0.0005, respectively) and with advanced stage disease (P < 0.0001 for both factors). Moreover, impaired E-cadherin expression directly correlated with an extensive disease in carcinoids and in LCNEC (P = 0.02 and P = 0.04, respectively) and with node metastasis in LCNEC (P = 0.01). Levels of E-cadherin and beta-catenin were correlated with each other, consistent with an internal regulatory loop. Our results indicate that down-regulation of the E-cadherin-beta-catenin complex plays a role in NET progression.
Salon
C
C
Department of Thoracic Oncology, University Hospital, Grenoble, France.
Moro
D
D
Lantuejoul
S
S
Brichon Py
P y
Py
Drabkin
H
H
Brambilla
C
C
Brambilla
E
E
D015820:Cadherins / Q000096:biosynthesis*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators / Q000096:biosynthesis*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin