title: Intracellular presence of insulin and its phosphorylated receptor in non-small cell lung cancer.
abstract: Insulin has been known for a long time to influence the growth and differentiation of normal and transformed cells. In order to delineate the role of insulin specifically in non-small cell lung cancer (NSCLC), we have now searched by immunohistochemistry (IHC) for the presence of insulin in NSCLC samples. Among the 112 samples we studied, 30 were found to contain insulin, which was detected in the form of intracytoplasmic granula. Moreover, its expression significantly correlated with (a) the morphological/histopathological subtype of NSCLC, being more frequent in adenocarcinomas; (b) the grade of tumor differentiation, displaying an increase in low-grade carcinomas; (c) tumor size, occurring predominantly in smaller tumors; (d) the presence of phosphorylated, activated insulin receptor; (e) the median patient age, being present in relatively younger individuals. Furthermore and interestingly, surrounding atypical adenomatous hyperplastic areas and normal alveolar pneumocytes scored insulin-positive in some of the insulin-negative tumors. In addition, PCR exploration for insulin transcripts in some samples positive for immunoreactive insulin was negative, indicating a possibly exogenous origin for the intracellular insulin in our NSCLC cohort. Taken together, our data suggest that an intracellular insulin activity is important for the progression of low-grade human lung adenocarcinomas.
authors.affiliation: Department of Development of Therapeutic Programs, CRS, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mattarocci
authors.forename: Claudia
authors.initials: C
authors.lastname: Abbruzzese
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mileo
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.forename: Barbara
authors.initials: B
authors.lastname: Antoniani
authors.forename: Gabriele
authors.initials: G
authors.lastname: Alessandrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.forename: Armando
authors.initials: A
authors.lastname: Felsani
authors.forename: Razvan T
authors.initials: RT
authors.lastname: Radulescu
authors.forename: Marco G
authors.initials: MG
authors.lastname: Paggi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000368:Aged; D000375:Aging / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D007328:Insulin; C435941:INSR protein, human; D011972:Receptor, Insulin