Vol.:(0123456789) 1 3 Clinical and Experimental Medicine https://doi.org/10.1007/s10238-017-0481-2 ORIGINAL ARTICLE Cytoplasmic expression of Twist1, an EMT‑related transcription factor, is associated with higher grades renal cell carcinomas and worse progression‑free survival in clear cell renal cell carcinoma Arezoo Rasti 1  · Zahra Madjd 1,2  · Maryam Abolhasani 1,3  · Mitra Mehrazma 1,3  · Leila Janani 4  · Leili Saeednejad Zanjani 1  · Mojgan Asgari 1,3 Received: 6 June 2017 / Accepted: 19 November 2017 © Springer International Publishing AG, part of Springer Nature 2017 Abstract Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial–mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical signifcance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defned renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas (pRCC) and 34 (13.5%) chromophobe renal cell car- cinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinico- pathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Signifcantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC sub- types, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These fndings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients. Keywords Twist1 · Epithelial–mesenchymal transition (EMT) · Renal cell carcinoma (RCC) · Prognosis · Tissue microarray (TMA) Introduction Renal cell carcinoma (RCC) is the most lethal genitourinary cancer that originates from the epithelium of renal tubules and comprises a group of tumor types including clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) [1, 2]. Annual estimates of newly diagnosed RCC cases have been increasing gradually over recent years, and up to 30% of RCC patients have metastases at the time of diagnosis [1, 3]. Although surgery is curative for the localized disease, a signifcant proportion of patients metas- tasize or relapse [4]. On the other hand, one of the impor- tant unmet medical needs in RCC is a prognostic biomarker enabling identifcation of patients at high risk of relapse after nephrectomy [5]. Therefore, studying the molecular mechanism of RCC metastasis helps to know the prognosis * Zahra Madjd zahra.madjd@yahoo.com * Maryam Abolhasani mar.abolhasani@gmail.com 1 Oncopathology Research Centre, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next TO Milad Tower, Tehran 14496-14530, Iran 2 Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran 3 Hasheminejad Kidney Center, Iran University of Medical Sciences, (IUMS), Tehran, Iran 4 Department of Biostatistics, School of Public Health, Iran University of Medical Sciences (IUMS), Tehran, Iran