Endometrial Cancer Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression Increases with Body Mass Index and Is Associated with Pathologic Extent and Prognosis

Abstract

Background Obesity is a main risk factor for endometrial carcinoma (EC). Insulin-like growth factor 1 receptor (IGF1R) expression may influence this association. Methods IGF1R IHC was performed on a tissue microarray with 894 EC and scored according to the percentage and intensity of staining to create immunoreactivity scores, which were dichotomized into low and high IGF1R expression groups. Logistic regression modeling assessed associations with body mass index (BMI), age, histology, pathologic extent of disease (pT), and lymph node metastasis (pN). Overall survival (OS) and disease-free survival (DFS) were compared between IGF1R expression groups using Kaplan–Meier curves and log-rank tests. Results The proportion of patients with high IGF1R expression increased as BMI (<30, 30–39, and 40+ kg/m2) increased (P = 0.002). The adjusted odds of having high IGF1R expression was 1.49 [95% confidence interval (CI), 1.05–2.10, P = 0.024] for patients with BMI 30 to 39 kg/m2 compared with <30 kg/m2 and 1.62 (95% CI, 1.13–2.33, P = 0.009) for patients with BMI 40+ kg/m2 compared with <30 kg/m2. High IGF1R expression was associated with pT and pN univariately and with pT after adjusting for BMI, pN, age, and histologic subtype. DFS and OS were better with high IGF1R expression, P = 0.020 and P = 0.002, respectively, but DFS was not significant after adjusting for pT, pN, and histologic subtype of the tumor. Conclusions There is an association between BMI and EC IGF1R expression. Higher IGF1R expression is associated with lower pT and better DFS and OS. Impact These findings suggest a link between IGF1R EC expression and obesity, as well as IGF1R expression and survival.

Incidence of Lymph Node Metastases in Women With Low-Risk Early Cervical Cancer (<2 cm) Without Lymph-Vascular Invasion

“…In accordance with studies in other types of tumors such as endometrial or thyroids cancer, 26,27 our study identified high BMI as an independent predictor factor of lymph node metastasis. Even though the mechanism to explain this finding is still unclear in the literature, 28 some authors have found that high insulinlike growth factor 1 receptor expression increased as BMI increased.…”

“…Overexpression of insulinlike growth factor 1 31 28 SC IB1 2 20 12 17 1 Not performed 2 54 29 AC IB1 2 11 1 28 1 Not performed 3 41 24 SC IB1 2 12 3 26 1 Not performed 4 40 26 SC IB1 2 10 1 19 1 Micrometastasis at SLN 5 50 31 SC IB1 3 18 8 16 1 Not performed 6 69 29 SC IB1 3 10 4 23 1 Not performed 7 44 32 SC IB1 2 4 3 16 1 Not performed 8 51 30 SC IB1 2 20 1 30 1 Macrometastasis at non-SLN 1 receptor has been found to be independently associated with tumor size, lymph node metastasis, and progression-free survival and overall survival in women with endometrial cancer. 26 In addition, a retrospective cohort study of 3086 women with cervical cancer observed that obesity was an independent prognostic factor for nodal metastasis and death. 29 A recent American Society of Clinical Oncology statement supports avoiding lymphadenectomy in patients with stage IB1 cervical cancer diagnosed in areas of low resources.…”

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA

“…Somewhat similar conclusions were obtained by Petridou et al, who suggested a more pronounced role of IGF2 than IGF1 in the etiology of EC [57]. Of clinical relevance, Price et al noted that increased IGF1R expression is linked to higher BMI and better overall survival and disease-free survival in EC [62]. Gunter et al observed that free IGF1 levels were inversely associated with the incidence of EC [63].…”

The Microcystic, Elongated, and Fragmented (MELF) Pattern of Invasion

“…This was done at the expense of having lower counts (16 cases with positive nodes, 5 DOD, 6 AWD) than could otherwise easily be obtained at our institution. 2 As a result, our analysis of non-vaginal recurrences and other adverse outcomes is very limited, without thorough multivariable conclusions. Moreover, a majority (13/16) of patients with positive nodes received adjuvant chemotherapy and or radiotherapy, complicating extrapolation of our findings to women who may have had only hysterectomy and for whom additional therapy is being considered.…”