Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer.
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.
Chakravarty
Geetika
G
Department of Pharmacology, Tulane University Health Science Center, School of Medicine, New Orleans, LA 70112, USA. geetikac@tulane.edu
Santillan
Alfredo A
AA
Galer
Chad
C
Adams
Henry P
HP
El-Naggar
Abdal K
AK
Jasser
Samar A
SA
Mohsin
Sayed
S
Mondal
Debasis
D
Clayman
Gary L
GL
Myers
Jeffrey N
JN
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
D017526:Receptor, IGF Type 1