Expression of survivin in squamous cell carcinoma and transitional cell carcinoma of the urinary bladder: A comparative immunohistochemical study

PURPOSE: To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index. RESULTS: Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.

Expression of CD 44 and MIB-1 in serous and mucinous ovarian tumors

In ovarian cancer, alterations in the extracellular environment are critical for tumor Initiation, progression and intra-peritoneal dissemination. Some markers have been used to study the progression of ovarian tumors, one of them is CD44 which shown to play critical roles in ovarian ameer metastasis. Tumor proliferation is known to be important factor in tumor growth. This can be measured by assessment of expression of MIB-1 protein in the tumor cells. To examine the immunohistochemical expression of CD44 and MIB-1 in a spectrum of serous and mucinous ovarian tumors [benign, borderline and malignant tumors] and to evaluate the correlation between intensity of markers expression with relevant clinicopathological criteria [Age, size, hilaterality, gross picture and stage]. Immunohistochemical staining of 120 samples [65 benign, 10 borderline, 30 malignant and 15 metastatic deposits] of spectrum of serous and mucinous ovarian tumors for CD44 and MIB-1 was performed using tissue microarray [TMA] and statistical analyses was done with SPSS [chi-square test]. In whole tumors, expression of [1] 44 in tumor cells [CD-44-T] was low in 20[80%] and high in 5[20%] of benign tumors, low in [70%] and high in 3[30%] of borderline tumors, and low in 24 [83%] and high in 5[17%] of malignant tumors with no significant association in transition from benign to malignant tumours [P 0.70]. Stromal CD44 [CD-44-S] expression was low in 33[94%] and high in 2[6%] of benign mmors, low in 8[80%] and high in 2[20%] of borderline tumors and low in 23[77%] and high in [23%] of malignant tumors with significant association in transition from benign to borderline to 14[CD44-M] showed reactivity in 9[25%] of benign tumors,5[50%] of borderline tumors and 21[72%] of malignant tumors with high significant association in transition from benign to malignant tumors [P<0.001]. In whole tumors, twenty three specimens [31%] showed high PI. All benign tumors had low PI. High significant association was detected between high PI and transition from benign to borderline to malignant tumors [P<0.001] with significant positive correlation between MIB-1 and CD44-M [P 0.013]. Our findings indicates that stromal and membranous expression of with transition from benign to borderline to malignant tumor, so increase in CD44 may play an important role in tumor progression and can be a target of more effective therapies

Pattern of human epidermal growth factor receptor 2 [HER2] expression in invasive breast carcinoma, immunohistochemical - study on patients in Upper Egypt

Breast cancer is a major public health problem throughout the world. It accounts for 38% of all new cancer cases among women living in Egypt. One of the most important prognostic and determinant factor of the line of its treatment is the human epidermal growth factor receptor 2 [HER2], it is associated with the more aggressive phenotype. Attention has been focused on the expression of HER2 receptor proteins in breast cancer cells especially its membranous domain, it resulted in variable results concerning its percentage of expression as well as its geographic distribution. So there is a need to study HER2 types of expression in breast cancer patients in our location as well as its correlation with the clinicopathological parameters. HER2 expression in 336 retrospective breast cancer specimens was examined immunohistochemically using tissue microarray. Expression was scored into 0, 1, 2 and 3 degrees and was correlated with clinicopathological criteria. HER2 expression in our specimens showed both membranous and cytoplasmic staining patterns. 18.6% of specimens showed membranous immunoreactivity and 74.1% specimens showed cytoplasmic staining pattern. Significant statistical association was found between cytoplasmic staining of HER2 and tumors of low grade, ER positivity [p<0.001, 0.001, 0.008] respectively. There was statistical significance difference between high membranous expression of HER2 and ER negativity [p=0.038], but our results didn't find significant difference with tumor size, lymphvascular invasion or lymph node metastasis. The frequency of high membranous expression of HER2 in our specimens is 18.6% and inversely correlated with ER positive tumors. This group of patients should be subjected to specific treatment with Trastuzumab, to improve their survival. Surprisingly cutoplasmic expression detected in most of our patients with frequency of 74.1% with positive relationship to low tumor grade and hormone receptor positive tumors. Since this group of patients may be resistant to trastuzumab and need specific treatment with tyrosine kinase drug inhibitors, this observation is going to be discussed and need to be followed up in the future

effect of omega-3 on renal functions and structure in experimental hyperthyroidism: possible role of angiotensin-converting enzyme 1

Hyperthyroidism is associate with reduced serum creatinine and urea, renal hypertrophy and eventually chronic renal disease. The aim of the present study was to investigate the potential therapeutic value of omega-3 on renal functions and structural changes induced by hyperthyroidism and the effect of omega-3 on angiotensin-converting enzyme 1 [ACE1] as a possible mechanism. Thirty rats were randomly divided into three groups. Control group received the vehicle. Hyperthyroid group was treated with L-thyroxine 0.1 mg/kg/day for 6 weeks and hyperthyroid-omega-3 treated group received L-thyroxine 0.1 mg/kg/day alone for 2 weeks followed by concurrent treatment with L-thyroxine 0.1 mg/kg/day and 3 g/kg/day omega-3 orally for 4 weeks. Serum creatinine, blood urea nitrogen [BUN], serum total antioxidant capacity [TAC], renal ACE1 and kidney weight to body weight [KW/BW] ratio were determined. Histopathological studies using H and E, Masson trichrome were done. Administration of L-thyroxine induced a significant decrease in serum creatinine, BUN and TAC and a significant increase in renal ACE1 and KW/BW ratio. Moreover, renal cortex thickness was increased, glomerular capillaries were congested with an increase in mesangial matrix. Proximal convoluted tubules [PCTs] were degenerated with no structural changes were observed in distal convoluted tubules [DCTs], afferent and efferent arterioles. Omega-3 administration is nearly normalized serum creatinine, BUN, TAC and renal ACE1 levels and ameliorates L-thyroxine-induced renal hypertrophy, glomerular congestion and PCTs degenerative changes. In conclusion, omega-3 administration has protective effects against hyperthyroidism-induced functional and structural changes. These reno-protective effects are possibly mediated by reducing ACE1 activity and its antioxidant activity