title: Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer.
abstract: Overexpression of insulin-like growth factor-I receptor (IGF-IR) is seen in a multitude of human thyroid cancers and correlates with poor prognosis. However, recent studies suggest that low phospho-IGF-IR (pIGF-IR) expression rather than its overexpression may be an indicator of poorly differentiated disease. No previous study has evaluated the expression of pIGF-IR to determine if activation or loss of expression of this receptor is associated with thyroid tumor progression. Accordingly, a quantitative immunohistochemical (IHC) method was used to evaluate the clinico-pathological significance of pIGF-IR expression in archival samples of human thyroid carcinomas. Quantitative analysis of pIGF-IR levels revealed a significant difference in the median index of pIGF-IR between different histological subtypes of thyroid cancer (P < 0.001). Specifically, the median pIGF-IR index of differentiated thyroid cancers was significantly higher than the median index of other poorly differentiated thyroid cancer (P < 0.001). This was further confirmed in individual tumor sections of thyroid carcinoma where anaplastic and differentiated components co-existed. No significant difference was noted in the pIGF-IR index of tumors grouped by size or stage but a trend towards lower mean pIGF-IR index was noted in older patients. Our data indicates that pIGF-IR is upregulated in a majority of follicular thyroid carcinomas, suggesting it may be a potential target for therapy for patients with this disease. In addition, since low pIGF-IR expression was found to correlate with aggressive human thyroid carcinoma, it also suggests that IGF-IR may not be needed for progression of anaplastic thyroid carcinoma possibly because other cell signaling pathways are activated, obviating the need for IGF-IR signaling. However, more mechanistic studies would be necessary to substantiate the possibility that pIGF-IR may be important for differentiation of thyroid tissues and is lost with disease progression.
authors.affiliation: Department of Pharmacology, Tulane University Health Science Center, School of Medicine, New Orleans, LA 70112, USA. geetikac@tulane.edu
authors.forename: Geetika
authors.initials: G
authors.lastname: Chakravarty
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Santillan
authors.forename: Chad
authors.initials: C
authors.lastname: Galer
authors.forename: Henry P
authors.initials: HP
authors.lastname: Adams
authors.forename: Abdal K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: Sayed
authors.initials: S
authors.lastname: Mohsin
authors.forename: Debasis
authors.initials: D
authors.lastname: Mondal
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: D000328:Adult; D000367:Age Factors; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D017526:Receptor, IGF Type 1