Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer.

BACKGROUND: Colorectal carcinoma (CRC) is the third most common human cancer. Twist, a basic helix-loop-helix (bHLH) transcription factor, is an epithelial-mesenchymal transition ((EMT) inducer that has been involved in carcinogenesis and chemoresistance. Also, the enhancer of Zeste homolologue2 (EZH2), a member of the polycomb group of genes, had been associated with poor prognosis in several malignancies. OBJECTIVE: To evaluate the expression of Twist1 and EZH2 in colon carcinoma in Egyptian patients and its relation to clinicopathological parameters, prognosis, and survival. METHODS: Twist1 and EZH2 expressions were evaluated immunohistochemically in 50 cases of colorectal tumors (12 colon adenomas and 38 colon carcinomas) and 20 samples from normal colonic mucosa. RESULTS: The expression of Twist1 and EZH2 was significantly higher in colon adenoma and carcinoma than that in normal colonic mucosa (P < 0.05). Twist1 and EZH2 expressions were associated with decreased tumor differentiation, advanced stage, and lymph node metastasis. Twist1 and EZH2 expressions were significantly related to 3-year disease-free survival (P = 0.005 and 0.002 respectively) and 3-year overall survival (P = 0.045 and 0.039, respectively). CONCLUSIONS: Twist1 and EZH2 may serve as prognostic predictors for colon carcinoma and may have a potential role as therapeutic targets in patients with colon carcinoma in the future.

Ameliorative role of curcumin on copper oxide nanoparticles-mediated renal toxicity in rats: An investigation of molecular mechanisms.

The increasing role of copper oxide nanoparticles (CuO NPs) in many industries and their broad range of applications increase its potential toxic effects. Curcumin possesses a wide range of health benefits. This study aimed to evaluate the role of curcumin in attenuating CuO NPs toxicity in rat kidney. Thirty six animals were divided into five groups; control groups (I, II), curcumin group orally received curcumin 200 mg/kg bw, CuO NPs group orally gavaged 250 mg/kg bw CuO NPs and combined group orally gavaged curcumin and CuO NPs. Treatment was given for 3 months. Administration of CuO NPs revealed elevation in serum creatinine and blood urea nitrogen levels, elevated kidney and urine levels of kidney injury molecule-1, decreased catalase, superoxide dismutase activities, total sulfhydryl, reduced glutathione content, increased serum reactive oxygen species, tissue total oxidant status, lipid hydroperoxides, protein carbonyl, malondialdehyde, nitric oxide levels, increased interleukin-1ß, tumor necrosis factor-α, nuclear factor (NF-κB), and decreased heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) genes expression. Moreover, histopathological alteration in kidney structure was detected. Immunohistochemical-stained sections by caspase-3 reaction revealed apoptosis. Pretreatment with curcumin improved most of the adverse effects in rats treated with CuO NPs regarding oxidative stress and inflammatory indices in kidney, and kept histopathological- and immunohistochemical-stained sections near to normal. This study shows that curcumin administration attenuates the toxicity in the kidney of CuO NPs-treated rats through its antioxidant, anti-inflammatory, and antiapoptotic effects.

Diagnostic Utility of Immunohistochemical Expressions of IMP3 Versus DOG1 and p63 in Salivary Gland Tumors.

OBJECTIVE: The diverse site of origin and classification complexity of salivary glands tumors increase difficulties in their diagnosis. This study aimed to evaluate the specificity and diagnostic ability of immunohistochemical expressions of IMP3 versus DOG1 and p63 in cases of such tumors. MATERIAL AND METHOD: Thirty paraffin-embedded salivary gland tumors were obtained from the Pathology Department Archive. Their diagnosis was confirmed. The specimens were then re-classified and evaluated using the IMP3, DOG1 and p63 immunohistochemical markers. RESULTS: There were 8 pleomorphic adenoma (PA), 12 mucoepidermoid carcinoma (MEC) and 10 adenoid cystic carcinoma (ADC) cases. All 12 MECs (100%) were IMP3 positive, while 30% of ADCs and only 25% of PAs were positive for IMP3. There was a statistically significant relationship between salivary gland tumors and IMP3 immunostaining (P =0.03). As regards to DOG1 results, 12.5% of PAs showed variable luminal positive immunostaining and 40% of ADCs showed weak luminal and abluminal immunostaining while 16.7% of MEC showed cytoplasmic staining. On the other hand, all ADCs (100%) showed moderate p63 reactivity in the nuclei of abluminal cells. All MEC cases (100%) were also p63-positive, showing a strong diffuse nuclear reactivity. A statistically significant relationship was noticed between salivary gland tumors and p63 immunostaining (P < 0.05). CONCLUSION: IMP3 is more sensitive for diagnosis of MEC than ADC. p63 is statistically significant in diagnosing salivary gland tumors (MEC and ADC). On the other hand, DOG1 staining is not sensitive in diagnosis of studied malignant salivary gland tumors, limiting its diagnostic utility.

Clinicopathological characterization and prognostic implication of FOXP3 and CK19 expression in papillary thyroid carcinoma and concomitant Hashimoto's thyroiditis.

Papillary thyroid carcinoma (PTC) is considered the most prevalent thyroid malignancy. The association between Hashimoto's thyroiditis (HT) and PTC is still unclear. We aimed to examine the clinicopathological impact of immunohistochemical staining of FOXP3 and Cytokeratin 19 in PTC and concomitant HT and their correlation with patients' outcome and survival. Eighty thyroid biopsies obtained from patients with PTC were immunostained by FOXP3 and CK19.The patients were treated by radioactive iodine (I131) and followed up. FOXP3 and CK19 expression were detected in 45% and 80% studied cases of PTC respectively. 16.7% of PTC with associated HT showed FOXP3+ lymphocytes in lymphocytic infiltrate of HT, while most of PTC associated HT express cytoplasmic CK19 positive Hurtle cells. FOXP3 was more expressed in PTC female patients more than 45 years with higher stage, lymph node, and distant metastasis, extracapsular extension, number of I131doses, and cumulative radioiodine doses with a highly statistically significant difference (p < 0.001). The relation was significant between CK19 immunostaining as regard 10-year Overall Survival and death (p value = 0.027 and 0.036, respectively). HT represents a step in the process of autoimmune inflammatory disease ending by the evolution of PTC with better prognosis, therefore appropriate follow up of these cases is needed. FOXP3 tends to be more expressed in PTC cases with worse prognostic variables and is predictable to become a recent prognostic and targeted therapy for PTC. There was a significant relation between CK19 immunostaining and 10 year overall survival.

Immunohistochemical Study of Glypican-3 and HepPar-1 in Differentiating Hepatocellular Carcinoma from Metastatic Carcinomas in FNA of the Liver.

Hepatocellular carcinoma (HCC) remains a common malignant cancer worldwide, it is considered the fifth most common malignant cancer. On the other hand, metastatic tumors are widespread in the liver , with metastatic adenocarcinoma (MA) constituting the greatest part, therefore differentiation of HCC from MA is a frequent problem facing the pathologist especially in liver fine-needle aspiration biopsies. Evaluating the diagnostic value of glypican-3 (GPC-3) and HepPar-1 immunostaining in differentiating hepatocellular carcinoma from metastatic tumors in liver cell block material. Fourty eight cell blocks prepared from FNA from the liver ( 30 cases HCC, 18 cases metastatic carcinoma in liver) stained by Glypican -3 and HepPar-1 immunohistochemical markers. Glypican-3 was immunoexpressed in 97% of cases of HCC while all cases of metastatic carcinoma were negative. HepPar-1 was expressed in 93% of cases of HCC and 11% of metastatic carcinoma of the liver. In this study the sensitivity of GPC3 in the diagnosis of HCC in cytological material was 96.7% and the specificity was 100% while the sensitivity and specificity of HepPar-1 was 93.3% and 88.9% respectively. Immunohistochemical staining for GPC-3 in cell block material of the liver is highly sensitive and specific and it is a valuable tool capable of differentiating HCC from most of metastatic tumors of the liver.

Immunohistochemical expression of HBME-1 and galectin-3 in the differential diagnosis of follicular-derived thyroid nodules.

BACKGROUND: Thyroid nodules are common among adults with only a small percentage being malignant and histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management. The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histological findings. Therefore, affected patients are referred for surgery, although only 10% will have a final diagnosis of malignancy. The aim of this study was to investigate the ability of two immunohistochemical (IHC) markers; galectin-3 and Hector Battifora mesothelial-1 (HBME-1) individually or in combination, to distinguish between benign (non-neoplastic and neoplastic) and malignant (follicular and papillary carcinomas) thyroid lesions removed by surgical resection. METHODS: We investigated the immunoexpression of galectin-3 and HBME-1 in 50 cases of benign and malignant thyroid nodules. The benign group included 13 cases of thyroid nodular goiter (NG) and 9 cases of follicular adenoma (FA). The malignant group included 5 cases of follicular thyroid carcinomas (FC), 18 cases of classic papillary thyroid carcinoma and 5 cases of follicular variant papillary carcinoma (FVPC). RESULTS: The staining results showed that malignant tumors expressed galectin-3 and HBME-1 significantly more than benign nodules. The sensitivity of these markers for the distinction between benign and malignant lesions ranged from 89.3% to 92.9%. Co-expression of galectin-3 and HBME-1 was seen in 82.1% of carcinomas, but in none of the benign nodules. Immunoexpression was usually diffuse in malignant tumors, and focal in the benign lesions. CONCLUSION: Our findings indicate that these immunohistochemical markers are significantly more expressed in malignant tumors compared to benign lesions and may be of additional diagnostic value when combined with routine histology. Galectin-3 has higher sensitivity and specificity of immunoexpression in thyroid malignancy than HBME-1, and the combined use of galectin-3 and HBME-1 can increase the specificity of immunoexpression in malignant tumors.