Alternative tyrosine phosphorylation of signaling kinases according to hormone receptor status in breast cancer overexpressing the insulin-like growth factor receptor type 1

Abstract

The insulin-like growth factor receptor type 1 (IGF1R) is suggested to play important roles in cancer cell growth through cross-talk with hormone receptors and growth factor receptors. However, its clinical significance in breast cancers in vivo is still unclear. We examined immunohistochemically the expression of IGF1R, phosphorylated-AKT (pAKT) and phosphorylated-ERK1/2 (pERK1/2) using tissue microarray slides containing 150 cases of primary breast carcinoma. Their mutual correlation and correlation with the status of hormone receptors epidermal growth factor receptor and human epidermal growth factor receptor type 2 were also investigated. IGF1R overexpression was detected in 71 cases (47%), and was correlated with lower nuclear grade (P = 0.03), positive estrogen receptor (ER) and/or progesterone receptor status (P = 0.002). pERK1/2 expression, detected in 53 cases (35%), was correlated with positive ER (P < 0.0001) and lower nuclear grade (P = 0.014). pAKT expression, detected in 88 cases (59%), was not correlated with nuclear grade, hormone receptors status or other clinical parameters. Of the 71 IGF1R-overexpressing tumors, pERK1/2 expression was detected in 27 (56%) of 48 ER-positive cases but in only four (17%) of 23 ER-negative cases (P = 0.022). In contrast, pAKT expression was constantly (64% or higher) detected irrespective of hormone receptor status in IGF1R-overexpressing breast cancers. Taken together, these findings suggest that IGF1R overexpression might activate pERK1/2 and pAKT in hormone receptor-positive breast cancer, but activate only pAKT in hormone receptor-negative breast cancer.

Figure 1

Immunohistochemical staining of insulin‐like growth factor receptor type 1 (IGF1R) protein in primary breast cancer scored according to area and intensity of membrane and cytoplasmic staining. (A) 0, (B) 1+, (C) 2+, (D) 3+ (×200). pERK1/2 staining was evaluated according to the intensity and proportion of nuclear staining. (E) 0, (F) 1+, (G) 2+ (×200). pAKT staining was evaluated according to the intensity and proportion of cytoplasmic staining. (H) 0, (I) 1+, (J) 2+ (×200).