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

Bioactive hyaluronan fragment (hexasaccharide) detects specific hexa-binding proteins in human breast and stomach cancer: Possible role in tumorogenesis.

Hyaluronan (HA) is a component of extracellular matrix that influences cell-proliferation, migration, development, regeneration, normal tissue remodeling, tissues undergoing malignancy and tumor cell interaction. The widespread occurrence of HA binding proteins, their involvement in tissue organization and the control of cellular behavior are well documented. The low molecular mass HA fragments can also induce a variety of biological events, including chemokine gene expression, transcription factor expression and angiogenesis. It is believed that these fragments are more potent in cellular activities than high molecular mass HA. In this study, we isolated the various fragments by gel permeation chromatography of hyaluronidase digested HA and characterized by fluoro assisted carbohydrate electrophoresis (FACE) and matrix assisted laser desorption ionization analysis (MALDI). Detection and distribution of cellular receptors in invasive tumor tissues for HA polymer and HA fragments were determined both by Western blot and histochemistry. The study demonstrated the overexpression of HA-hexa binding protein in human tumors of breast and stomach and its involvement in tumorogenesis.

CD44V6 and K167 expression in nodal and disseminated

CD44 is a multifunctional cell surface adhesion molecule family, expressed in many cell types. High expression of the standard CD44s and its variant form CD44v6 has been reported to be associated with tumor dissemination in non Hodgkin 's lymphoma The aim of this study was to evaluate the expression of CD44v6 and Ki67 in disseminated and localized nodal B-cell lymphomas, and their relation to tumor histopathological grading and clinical staging. We examined 70 cases of B-cell NHL [36 disseminated, stages IlI IV and 34 nodal, stages I, H]for expression of CD44v6 and Ki67 immunohistochemically. We found that CD44v6 was expressed in [18/70 cases, 25.7%] of the studied group with 14 cases from the CD44v6 positive cases of the diffuse large B-cell lymphoma type, p<0. 005]. Ki67 was expressed in [58/70 cases, 82.8%] of the studied cases with [48 Ki67 positive cases] of the diffuse large B-cell lymphoma type, p<0.005]. We concluded that CD44v6 expression is associated with lymphoma cell dissemination, advanced clinical stage and high histological grading

Expression of CD44 protein and cytokeratin 20 in non Bilharzial and Bilharzial bladder carcinoma

Carcinoma of the urinary bladder is one of the most common cancers world wide. It is the fourth most common malignancy in males and the ninth most common malignancy in females. CD44 is a family of cell-surface transmembrane glycoproteins that serve as receptors for hyaluronate and bind extracellular matrix components. CD44 plays a definite role in cell- cell and cell- matrix interactions. Thus, its down-regulation would facilitate loss of cell - cell cohesion, detachment from the basement membrane, and subsequent infiltration of the underlying tissues. It is suggested that the expression of CD44 is associated with differentiation and prognosis in bladder carcinoma. Cytokeratins [CKs] are a family of proteins that form the intermediate filament cytoskeleton of epithelial cells. Cytokeratin 20 [CK20] has been proposed as a marker of neoplastic change as well as a predictor for progression of urothelial carcinoma. The aim of the work is to study the immunohistochemical expression of CD44 and CK20 in carcinoma of the urinary bladder and correlate the immunohistochemical expression of CD44 and CK20 with different prognostic parameters including the grade and stage of the studied tumors. The studied 71 specimen were subjected to the ordinary H and E staining and immunohistochemical staining for CD44 and CK20. Correlative studies between CD44 and CK20 expression with different prognostic parameters including the grade and stage of the studied tumors revealed statistically significant correlation between CD44 and CK20 expression and the tumor grade and stage of urothelial carcinoma cases. No relation was found between the expression of CD44 and CK20 and the presence of Bilharziasis. Loss or reduction of CD44 immunoreactivity and increasing CK20 positiviiy were significantly associated with increasing tumor grade and stage in the studied cases of urothelial carcinoma and to each other, so, they have combined utility in predicting the behaviour and prognosis of urothelial carcinoma, with no significant difference in their expression between non Bilharzial and Bilharzial bladder carcinomas

Correlation of serum level of homing cell adhesion molecule [HCAM, sCD44] with clinical features and prognosis in systemic sclerosis

To evaluate the level of Homing Cell Adhesion molecule [H-CAM, sCD44] in the sera of systemic sclerosis [SSc] patients and to investigate its relationship to clinical and prognostic features of the disease. This prospective study was conducted on 30 SSc patients; 18 with limited cutaneous SSc [lSSc] and 12 with diffuse cutaneous SSc [dSSc]. Twenty apparently healthy subjects participated to the study as controls. Clinical evaluation and pulmonary function tests were done for all of them. Laboratory investigations and serum levels of soluble CD44 [sCD44] were determined using specific enzyme-linked immunosorbent assay [ELISA] for all patients and controls. Serum concentration of sCD44 was significantly elevated in SSc patients as compared with controls [1.89 +/- 0.72 vs. 1.42 +/- 0.33 ng/ml, p<0.001]. This elevation was observed in 43% of SSc patients; in 50% with lSSc patients but only 33% in dSSc patients. In addition, serum sCD44 levels were significantly elevated in patients with lSSc when compared with those with dSSc patients and both were significantly higher than controls [2.06 +/- 0.62 vs. 1.67 +/- 0.25 ng/ml, p < 0.001 and p < 0.02 respectively]. A significant correlation was found between elevated sCD44 levels and the extent of skin sclerosis as determined with Modified Rodnan Skin Score [r=0.670 and p<0.001]. It was also found that the prevalence of pulmonary fibrosis and decreased FVC% and FEV1% in SSc patients with elevated sCD44 levels were significantly lower than in those with normal sCD44 levels [15 vs. 51%, p <0.001; 16 vs. 56%, p <0.001 and 28 vs. 64%, p<0.001 respectively]. Furthermore, the prevalence of pulmonary fibrosis was significantly lower in ISSc with elevated sCD44 levels than in those with normal levels [22% vs. 56%, p<0.001]. Although the disease duration was similar for SSc patients with elevated sCD44 levels and those with normal levels, the disease duration in ISSc patients with elevated sCD44 levels was significantly shorter than in patients with normal sCD44 levels [4.1 +/- 6.6 vs. 7.1 +/- 9.4 yrs; p<0.01]. Elevation of serum concentration of sCD44 and its prevalence was more in the limited form of SSc [ISSc]. This elevation correlated significantly with the shorter disease duration in patients with ISSc. Furthermore, elevated sCD44 levels were also associated with lower prevalence of pulmonary involvement and better pulmonary function in SSc patients. This was observed even in patients with ISSc. Taken together, these results suggest that the elevation of sCD44 may be a prognostic marker and protective factor for the development of skin sclerosis and pulmonary fibrosis in SSc

Clinical relevance of soluble CD44 in serum as indicator of tumor burden in patients with B-lymphoid malignancies

In this study, the serum level of sCD44 was studied in a group of B- lymphoid malignancies at presentation trying to define any association with tumor burden and clinical staging and to correlate the soluble marker with other clinical, laboratory and biologic parameters. It was conducted on 100 adult patients with different B-lymphoid malignancies divided into two groups. ELISA determinations revealed a significant elevation of serum sCD44 values in the entire patients group and the three subgroups of lymphoma/leukemia as well as HD group in comparison with the controls. On comparing the three subgroups as regards sCD44 mean values, a significant difference was observed with the least mean value expressed by the highly aggressive subgroup. 68% of the studied patients showed serum sCD44 above the cut-off value and 16% showed levels above 1000 ng/ml