c-MET expression in colorectal adenomas and primary carcinomas with its corresponding metastases.

BACKGROUND: c-MET plays an important role in tumor proliferation, invasion and metastasis. In this study we examined the expression of c-MET in colorectal adenomas, primary adenocarcinomas and their corresponding lymph node, peritoneal and liver metastases. We correlated our findings with clinicopathological features. METHODS: Twenty three cases of colorectal adenoma and 102 cases of primary colorectal carcinoma and their corresponding metastases (44 lymph nodes, 21 peritoneal deposits and 16 liver metastases) were studied to evaluate c-MET expression by immunohistochemistry. For comparison, 12 sections of adjacent healthy colorectal mucosa were examined. RESULTS: Statistically significant differences were present among normal tissues, colorectal adenomas and primary colorectal carcinomas (P=0.011). Normal tissues showed a negative or weak reaction in 66.67% and 33.33% of cases respectively. Expression of c-MET was positive in 47.8% of adenomas. A significant positive association was identified between c-MET high expression and degree of dysplasia (P=0.024). c-MET was highly expressed in 66.7% of primary colorectal carcinoma. Significant positive correlations were detected between c-MET expression and TNM stage (P=0.036), lymph node metastasis (LNM), peritoneal deposits and liver metastasis (P=0.038, P=0.094 and P=0.045, respectively). c-MET expression in metastatic tissues was significantly higher than that of the primary tumor. CONCLUSIONS: c-MET expression is gradually up-regulated in the development and progression of colorectal cancer (CRC) from normal epithelium to adenoma to colorectal carcinoma to metastases.

Does Immunohistochemistry for Discovered on GIST1 and Minichromosome Maintenance Protein7 Provide Additional Clinicopathological Value in Gastrointestinal Stromal Tumors?

BACKGROUND: The aim of the study was to investigate the expression of discovered on GIST 1 (DOG1) and minichromosome maintenance protein 7 (MCM7) in addition to the traditional markers, C-KIT and Ki-67, in gastrointestinal stromal tumors (GISTs) to specify the diagnosis and to evaluate their clinicopathological significance in GIST patients. METHODS: Hematoxylin and eosin sections of 43 GISTs were re-examined to review histopathological criteria and risk stratification of these tumors. Immunohistochemistry for DOG1, C-KIT, MCM7, Ki-67 antibodies was performed. RESULTS: Positive DOG1 and C-KIT expressions were found in 42 (97.7%) and 39 (90.7%) of cases, respectively. DOG1 and C-KIT expression scores were significantly correlated (P < 0.001). Among four C-KIT-negative GISTs, three cases were DOG1-positive. DOG1 was more sensitive and specific than C-KIT in the diagnosis of GISTs. High DOG1 expression scores were significantly associated with tumor size (P = 0.023) and risk (P = 0.037). Significant positive correlation was noted between MCM7 and Ki-67 labeling indices (LIs) (P < 0.001, r = 0.885). MCM7 demonstrated higher proliferation LIs than Ki-67. Significant associations were found between MCM7 and Ki-67 LIs and tumor size (P = 0.001 and 0.003 respectively), mitotic rate (P < 0.001 both) and risk stratification (P < 0.001 both) with a stepwise increase in MCM7 LIs with increasing tumor risk. CONCLUSION: DOG1 is an important diagnostic tool for GISTs particularly in C-KIT-negative tumors. It may have a role in GISTs tumorogenesis and progression. Despite the established clinicopathological value of Ki-67 in GISTs, detection of MCM7 expression is recommended as a prognostic adjunct, given its better sensitivity for cellular proliferation and stepwise association with tumor risk.

Utility of SOX2 and Livin Co-Expression in the Prognosis of Bladder Cancer With Bilharzial and Non-Bilharzial Bladder Status.

BACKGROUND: The aim of this study was to investigate the expression of SOX2, a key transcription factor and livin, an apoptotic inhibitor in bladder transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC). Moreover, their prognostic significance was assessed. METHODS: The expressions of SOX2 and livin in 82 TCC and 35 SCC cases were detected by immunohistochemistry. RESULTS: SOX2 and livin were over-expressed in tumor tissues as compared to the corresponding adjacent non-neoplastic tissues. SOX2 and livin expressions were significantly associated with high tumor grade (P = 0.002 and P = 0.007, respectively) and high tumor stage (P = 0.027 and P = 0.033, respectively). No significant correlation was found between tumor and other clinicopathological factors such as age, gender and schistosomal status. Univariate analysis revealed that TCC and SCC patients with high SOX2 or livin expressions were significantly related to overall survival (P < 0.001, P = 0.025 for TCC patients and P = 0.041, P = 0.021 for SCC patients, respectively). Multivariate survival analysis further demonstrated that SOX2 expression was an independent prognostic factor for TCC patients (P = 0.015). CONCLUSIONS: SOX2 and livin may contribute to the progression of bladder carcinoma. SOX2/livin pathway regulates cancer stem cell survival so it could be targeting as an effective therapeutic strategy for cancer treatment.

Expression of Snail transcription factor in prostatic adenocarcinoma in Egypt: correlation with Maspin protein expression and clinicopathologic variables.

BACKGROUND: Snail transcription factor and Maspin tumor suppressor serpin are involved in the regulation of progression, invasion and metastasis of many human malignancies. However, there is very limited data in the literature about their role in prostatic adenocarcinoma. The present study was designed to investigate Snail and Maspin expression, their interrelationship and their relationship to different clinicopathologic variables in clinically detectable prostatic adenocarcinoma. MATERIAL AND METHODS: Tissue sections from 110 resected prostatic lesions distributed as 80 cases of prostatic adenocarcinoma and 30 cases of benign prostatic hyperplasia (BPH) were evaluated for Snail and Maspin proteins expression by immunohistochemistry. RESULTS: Snail protein expression was detected in 53.8% of prostatic adenocarcinomas versus none of BPH cases (p = < 0.001). A significant positive correlation of Snail expression to cancer grade (p = 0.015), lymph node metastasis (p = 0.026) and pTNM stage (p = 0.036). Maspin expression was detected in 36.6% of prostatic adenocarcinomas versus 93.3% of BPH cases (p = < 0.001). A significant negative correlation of Maspin expression to cancer grade (p = 0.007) and lymphovascular invasion (p = 0.017). Also detected was a significant negative relationship between Snail and Maspin expression in cancer cases under investigation (p = 0.002). CONCLUSION: Snail immunohistochemical expression can be promising as a potential prognostic biomarker in prostatic adenocarcinoma since it was significantly associated with clinicopathologic variables of progressive disease. A potential role for Snail in regulating Maspin expression is suggested based on the finding of negative association between Snail and Maspin expression in prostatic adenocarcinoma.

Effect of acute immobilization stress with or without a heme oxygenase inducer on testicular structure and function in male albino rats.

BACKGROUND: Stress disturbs homeostasis and may induce various disorders. Immobilization stress (IS) induced due to reduced area provided for mobility results in the imbalance of oxidant and antioxidant status. Stress leads to male reproductive dysfunction in many species, including rodents and humans. Induction of heme oxygenase-1 (HO-1), the rate limiting enzyme in heme degradation, increases host antioxidant defenses. We elucidated the protective role of induction of HO-1 by hemin on testicular damage induced by acute IS. METHODS: Male albino rats were immobilized for a period of 6 h. Hemin was given for 3 consecutive days (40 µmol/kg/day, s.c.), before subjecting the animals to acute IS. RESULTS: Upregulation of HO-1 following hemin administration was evidenced in our study by increasing carboxyhemoglobin (COHb) level. Histopathological evaluation confirmed that acute IS caused significant testicular tissue injury, which improves in groups pretreated with hemin. Acute IS also caused significant increases in serum catecholamines and corticosterone levels; however, it produced a significant decrease in testosterone level with non-significant changes in luteinizing hormone (LH) level. In addition, it was found that IS significantly increased testicular malondialdehyde (MDA) and decreased catalase activities. The HO-1 inducer (i.e., hemin) significantly decreased catecholamines and corticosterone levels, and increased testosterone and LH levels. Hemin also decreased testicular MDA and increased catalase activities significantly. CONCLUSIONS: Induction of HO-1 protects the testes through its antioxidant and anti-inflammatory effects. Thus, it represents a potential therapeutic option to protect testicular tissue from detrimental effects of IS.