Arezoo Rasti - Oncopathology Research Centre, Iran University of medical Sciences (IUMS),Tehran, Iran
Mitra Mehrazma - Hasheminejad Kidney Center, Iran University of Medical Sciences, (IUMS),Tehran, Iran
Zahra Madjd - Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
Maryam Abolhasani - Oncopathology Research Centre, Iran University of medical Sciences (IUMS),Tehran, Iran

Purpose Twist is a key transcription factor which confers tumor cells with cancer stem cell (CSC)-like characteristics and has been reported to significantly enhance epithelial-mesenchymal transition (EMT) under various pathological conditions including tumor malignancy, invasion and metastasis. This study aimed to evaluate the expression patterns and clinical signiï پcance of twist as an EMT related transcription factor in renal cell carcinoma (RCC). Methods The nuclear and cytoplasmic expression of twist was examined in 252 well-deï پned renal tumour 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 carcinomas (ChRCC), by immunohistochemistry on a tissue microarray(TMA). The association between expression of this marker and clinicopathologic parameters was then analyzed. Results Twist Immunohistochemistry (IHC) staining was observed as cytoplasmic or nuclear expression but it was mainly localized to the cytoplasm of tumour cells. There was a signiï پcant difference in the nuclear expression levels of twist in the ccRCC samples compared to the ChRCC and pRCC samples (respectively P <0.001 and P =0.001) and a signiï پcant difference in the cytoplasmic expression levels of twist in different tumor grades (P =0.05). Nuclear expression of twist was significantly correlated with tumour stage (P =0.05).No significant association was found between nuclear and cytoplasmic expression of twist and clinicopathologic parameters including regional lymph node & renal vein involvements, tumour size, microvasulcar invasion (MVI) and metastasis to the Gerota’s fascia,adrenal gland, peripheral fat, and renal pelvis. Conclusion Significantly higher nuclear and expression levels of twist were found in pRCC and ccRCC samples. Evaluation of nuclear expression of twist demonstrated the significant positive correlation between tumour type and stage of disease.The difference between the mean cytoplasmic expression of twist in grade III in comparison grade I and II was significant. Increased nuclear expression of twist was associated with more aggressive tumour behavior in RCC patients, especially in pRCC and ccRCC subtypes due to their more metastatic behavior. These findings suggest that both nuclear and cytoplasmic expression of twist can be considered as a diagnostic and therapeutic marker for targeted therapy of renal carcinoma.

Twist , epithelial-mesenchymal transition ,Cancer stem cells (CSCs), Renal cell carcinoma (RCC), Tissue microarray (TMA)