High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer

abstract

HMGA2 is a small, non-histone, chromatin-associated protein with a key role in tumorigenesis and adipogenesis. Indeed, HMGA2 overexpression has been frequently detected in several malignant neoplasms and inhibition of its expression prevents thyroid cell transformation. Moreover, HMGA2 null mice show a pigmy phenotype with a great reduction in fat tissue. To investigate whether HMGA2 expression correlates with clinico-pathological parameters and patient outcome, immunohistochemical analysis of HMGA2 expression was performed in ovarian cancer specimens from 117 patients. HMGA2 overexpression was found in 39% of the cases and, interestingly, positively correlated with the body mass index (BMI). Moreover, high BMI (≥ 25 kg/m(2) ) and high HMGA2 expression/BMI combined evaluation predicted shorter disease-free survival. High BMI (≥ 25 kg/m(2) ), high expression of HMGA2 and high HMGA2 expression/BMI combined evaluation predicted shorter overall survival. In multivariate analysis, the concomitant high expression of HMGA2 and high BMI (≥ 25 kg/m(2) ) was an independent prognostic factor. Finally, the BMI (≥ 25 kg/m(2) ) negatively correlated with the patient response to chemotherapy (P=0.039). Therefore, the data reported herein suggest that the combined evaluation of HMGA2 expression and obesity assessed through BMI can be considered a marker of poor prognosis in patients affected by ovarian carcinoma