Immunohis1ochemical cyclooxygenase-2 [COX-2] and cd31 expression in breast carcinoma with correlation to clinico-pathological parameters

Breast cancer is the most'common cancer in Egyptian women. COX-2 seems to be involved in malignant transformation and tumor progression by affecting cell proliferation, mitosis, cell adhesion, apoptosis, immune surveillance, and angiogenesis. Angiogenesis is an important key step in tumor progression. Microvascular density [MVD], a surrogate marker of angiogenesis can be assessed by CD31 staining. This study aims to: 1. Evaluate COX-2 and CD31 expressions in breast cancer. 2. Determine the correlation between COX-2 and CD31 with the clinico-pathological parameters in ductal breast carcinoma. This study included 74 specimens of breast lesions. Patient's age, tumor size and local aggressive changes, history of recurrence and/or presence of distant metastasis were obtained. Hematoxylin and Eosin [HandE] stained sections were evaluated for histopathological tumor type, tumor grade, presence or absence of normal hyperplastic, in situ component, lymphocytic infiltration, lymphovascular invasion, and axillary lymph node status. COX-2 and CD31 immunostaining was done to detect their expression using the avidin-biotin peroxidase method. COX-2 increased with increasing grade of ductal carcinoma in situ [DC1S] and invasive ductal carcinomas [IDC] [P< 0.05 and P< 0.002 respectively]. COX-2 expression increased progressively along the continuum of neoplastic changes from normal breast epithelium to IDC [P< 0.01]. There was significant correlation between COX-2 and tumor size [P< 0.05], tumor grade [P< 0.002], lymphovascular invasion [P< 0.03] and lymph node metastasis [P< 0.02]. CD31 staining was observed along the cell membrane of endothelial cells of microvessels in all breast specimens. The median CD31 MVD count was 10 for normal breast, increased insignificantly to 17 in hyperplastic lesions, and reached 19 for DCIS, and 66.5 in IDC [P < 0.000]. There was significant increase in MVD between different grades of IDC [P < 0.01] but not in DCIS. Positive correlation was present between COX-2 and CD31 in DCIS and in IDC [P< 0.000 for each]. COX-2 was increased with poor prognostic parameters; tumor size, tumor grade, lymphovascular invasion and lymph node metastasis. CD31 increases with increasing grade of IDC. These findings might imply for new therapeutic strategies in order to prevent progression of DCIS to IDC and to improve cancer therapy

CD 117 tyrosine kinase receptor expression in gliomas

Gliomas are the most common primary brain tumors. Despite therapeutic advances, the majority of gliomas do not respond to either chemo or radiotherapy. CD117, the gene product of c-kit has been expressed in glial tumors. Because gastrointestinal stromal tumors [GISTs] that express CD117 respond dramatically to treatment with tyrosine kinase inhibitors, identification of glial tumors that express CD117 might open new therapeutic approaches for treatment of these tumors. This work was planned to study the role of CD117 [KIT] in the development and progression of gliomas mainly astrocytomas. Also, to assess if CD117 might serve as a biomarker for those gliomas that might respond to tyrosine kinase inhibitors. We studied 71 cases of gliomas. They were 59 astrocytomas, 9 ependymomas, 2 mixed oligoastrocytomas and single case of anaplastic oligodendroglioma. Paraffin embedded sections were immunostained using primary antibodies against CD117. Antigen antibody reaction was detected by streptavidin-biotin kit. In the present work, CD 117 immunoreactivity was noted in different grades of astrocytomas. The CD 117 average weighted scores showed gradual upregulation with increasing grade from pilocytic astrocytoma [16.7%]-diffuse astrocytoma grade II [33.3%]-anaplaslic astrocytoma [66.7%]-glioblastoma multiforme [79.3%.]. Majority of the gliomas [57.7%.] were found to express CD117 to varying degrees, and high grade tumors [78.6%] had a higher proportion of CD117 expression than low grade tumors [27.6%]. In 21.12% of studied cases, the CD117 was expressed in endothelial cells of tumor blood vessels. Twelve cases of them [80%] were most prominent in microvascular proliferations of high grade tumors and eleven cases of them showed strong intensity. High grade astrocytomas [especially glioblastoma multiforme] showed more frequent and strong expression of CD117, this indicate that CD]117 may has possible role in early astrocytoma tumorigenesis and in progression. Also, CD117 may serve as a biomarker for those gliomas that respond to tyrosine kinase inhibitor drugs

Evaluation of expression and prognostic values of survivin and Ki67 in bladder carcinoma

Survivin is a member of the inhibitor of apoplosis family that inhibit apoptosis controls mitotic progression and induces tumour cell invasion. Our objectives were to evaluate the association of survivin expression in the various types of bladder cancer and the clinical outcome. Immunohistochemical staining for survivin and ki67 was performed on 5 normal bladder and 51 patients: 9 cases had PNTCC [papillary non infiltrating transitional cell carcinoma], 16 had invasive TCC [transitional cell carcinoma], 10 had TCC with squamous differentiation and 16 had SCC [squamous cell carcinoma] among the 51 patients examined there were 10 known recurrent cases. Survivin and Ki67 were not expressed in normal bladder urothelium.Survivin was over expressed with higher tumour grade in both TCC [p=0.05] and SCC [p=0.04] and with high tumour stage in TCC [p=0.004]. Survivin expression might help identify patients of bladder carcinoma at high risk of disease recurrence and progression who would benefit from closer follow-up or more aggressive therapy

Expression of epidermal growth factor receptor-1 in chronic schistosomal urinary bladder lesions

Over expression of growth factors including epidermal growth factor receptor [EGFR], have been implicated in bladder cancer biology. This study was conducted in a trial to a better understanding the genetic mechanisms underlying the proliferative, the premalignant and malignant changes frequently displayed in chronic schistosomal cystitis [ChSC] and schitosoma associated carcinoma of the bladder. The study included 58 Egyptian patients [15 ChSC and 43 bladder cancer], and 5 normal urothelial specimens as control. The bladder cancer specimens were selected included adjacent normal mucosa or dysplastic areas [27 squamous cell carcinoma SCC and 16 transitional cell carcinoma TCC]. Level of expression of EGFR was analyzed using an immunohistochemical approach and the results compared with histological pattern, grading and pathological staging. In normal epithelium EGFR expression was only limited to the basal layer, but in dysplastic epithelium adjacent to tumour tissue all cells stained for EGFR. Bilharzial associated TCC exhibit very low expression, EGFR expression was weak cytoplasmic or even absent. The majority of SCC expressed strong membrane staining for EGFR and almost all cells were positive for the receptor. However, the intensity of staining was increasing with a significant statistical correlation with grade [p < 0.01] and with invasiveness of the tumour [p < 0.001]. In conclusion over expression of EGFR [high intensity] in human bladder cancer may be associated with poor differentiation and with invasion that could be implicated in the pathway of oncogenesis for schitosoma associated SCC of the bladder

Immunohistochemical study, in situ hybridization and computerized image analysis of colorectal epithelial progression from adenoma to carcinoma

This work aimed to study formalin fixed, paraffin embedded tissues from 60 cases of adenomas and 100 cases of carcinomas from patients who underwent surgery for the removal of colorectal adenoma and/or carcinoma in the VAPHS [Veterans Administration of Pittsburgh Healthcare System] and UPMC [University of Pittsburgh Medical Centre]. These cases included 28 adenomas with a definite evidence of progression to carcinoma. Proliferation and apoptosis in normal colonic mucosa, adenomas and carcinomas were determined and related to the expression of cell cycle and apoptosis associated proteins [Ki-67, bcl-2, bax and p53] using streptavidin biotin, in situ hybridization and computerized image analysis techniques. Bcl-2 expression reached its highest level in adenomas, followed by carcinomas, which displayed a higher level than adjacent normal mucosa in the same specimen. There was a progressive increase in bax, p53, Ki-67 and ApopTag labeling indices along normal-adenoma-carcinoma sequence. It was found that bax LI was significantly higher in large adenomas and p53 LI and Ki67 LI were significantly lower in tubular adenomas