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Chronic hyperinsulinemia due to insulin resistance and elevated levels of insulin-like growth factor (IGF)-1 and IGF-2 are suggestive of a significantly higher risk of endometrial carcinoma. There is a wealth of evidence showing differential expression of IGF-1 isoforms in various types of cancer. In the present study, 99 archived endometrial carcinoma tissue sections were retrospectively assessed by immunohistochemistry for IGF-1Ec isoform expression. Expression of IGF-1Ec was also assessed in nine cases of non-neoplastic endometrial tissue adjacent to the tumor, in 30 cases with normal endometrium and in 30 cases with endometrial hyperplasia. Furthermore, the association between IGF-1Ec and the concurrent expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53 or survivin was assessed, as well as their combined expression in association with clinicopathological variables. In endometrial carcinoma, IGF-1Ec expression was high in non-endometrioid carcinoma (serous papillary or clear cell carcinoma) compared with that in endometrioid adenocarcinoma. IGF-1Ec expression was also high in the presence of tumoral necrosis. Furthermore, there was a significant correlation between the histological differentiation and the sum of staining intensity and the number of IGF-1Ec immunopositive cells in endometrial carcinoma. There was a moderate negative correlation between co-expression of IGF-1Ec and PTEN, for both the number of immunopositive cells (P=0.006, ρ=−0.343) and the sum of staining (scores and intensity; P=0.006, ρ=−0.343). Furthermore, there was a positive correlation between the sum of staining (scores and intensity) and co-expression of IGF-1Ec and survivin (P=0.043, ρ=0.225). However, there was no association between concomitant expression of IGF-1Ec and p53. These results emphasized the importance of IGF-1Ec expression during development of non-estrogen dependent endometrial adenocarcinoma. IGF-1Ec and PTEN may function opposingly during endometrial carcinogenesis. By contrast, IGF-1Ec and survivin may share common molecular pathways and may promote, in parallel, tumoral development.

Immunohistochemical expression of insulin‑like growth factor‑1Ec in primary endometrial carcinoma: Association with PTEN, p53 and survivin expression