Role of Geminin and Mcm-2 in Prognosis of Renal Cell Carcinoma

Role of Immunohistochemical Markers , Geminin and Mcm2 in Prognosis of Renal Cell Carcinoma, and Its Clinicopathological Correlation. A Prospective Controlled Study

The study aim is to prospectively assess the prognostic significance of immunohistochemical markers Geminin and Mcm-2 in cases of renal cell carcinoma and to detect its clinicopathological correlation.

Renal cell carcinoma (RCC) is one of the most common urological malignancies. Approximately 338,000 people are diagnosed with RCC worldwide each year, representing approximately 2-3 % of all cancers. RCC can be classified into non-epithelial and epithelial, according to cell origin. The four major types are of epithelial origin includes: clear cell renal carcinoma (ccRCC), papillary, chromophobe renal carcinoma (chRCC) and collecting duct carcinoma. The most common subtype of RCC is ccRCC which accounts for approximately 70-80% of all renal cell carcinomas. Prognostic factors for RCC can be classified into: anatomical, histological, clinical, and molecular factors. Anatomical factors include tumor size, venous invasion, renal capsular invasion, adrenal involvement, Lymph node and distant metastasis. Histological factors include tumour grade, RCC subtype, sarcomatoid features, microvascular invasion, tumour necrosis, and invasion of the collecting system. Clinical factors include performance status, local symptoms, cachexia, anaemia, platelet count, neutrophil/lymphocyte ratio, C-reactive protein (CRP) and serum albumin. As regard the molecular factors, numerous markers such as carbonic anhydrase IX, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), Ki67, PTEN (phosphatase and tensin homolog), osteopontin and other cell cycle and proliferative markers are being investigated. The efficiency and accuracy of biomarkers studies using immunohistochemical and tissue microarray techniques are still variable and unclear in regards to prognostic significance in patients with renal tumors. Multiple biomarkers shown to be significant to assess diagnosis and prognosis in these patients and other were not significant. In the RCC cell cycle, minichromosome maintenance 2 (Mcm2), Geminin define the proliferative state. Investigators are able to determine differential levels of expression of various markers in normal tissue compared with indolent and aggressive tumors. Among platforms used in determining the presence of biological markers in surgical pathology specimens, immunohistochemistry is perhaps the most commonly available tool in the routine diagnostic laboratory. Immunohistochemistry allows detection of antigens expressed on tumor cells, hence permitting characterization of the tumor. This study was designed to assess the prognostic significance of Geminin and Mcm-2 in cases of renal cell carcinoma and to assess its clinicopathological correlation.

Group (A) [study cases] Adult patients who will undergo radical or partial nephrectomy.for primary renal cell carcinoma.

Histopathological study and evaluation: For each case, the tissue samples will be evaluated by the pathologist for detecting the histopathology and in cases of malignant renal spicemens the pathologist will also assess the histologic type, Fuhrman nuclear grade, cellular invasion of perinephric fat, and the extent of any vascular invasion seen by microscopy. Immunohistochemistry: Immunohistochemical staining will be performed by using the following antibodies: Geminin and Minichromosome maintenance-2 (MCM-2). Evaluation of the immunohistochemical staining will be performed by light microscopy. The interpretation of immuno-reactivity will be performed in a quantitative manner by analyzing the extent of the staining positivity of the tumor cells. Immuno-staining of greater than 10% of tumor cells is required for scoring as a positive case.

Number of patients that develops recurrent tumor after partial or radical nephrectomy as diagnosed by Multi slice CT will be assessed

Number of patients that develops tumor metastasis after partial or radical nephrectomy as diagnosed by Multi slice CT will be assessed

Inclusion criteria: Adult patients who will undergo radical or partial nephrectomy for primary Renal cell carcinoma (Group A). Adult patients who will undergo simple nephrectomy for benign causes (Group B). Exclusion criteria: Patients with secondary renal metastasis. Patients with metastatic spread at time of presentation or operation. Patients with renal urothelial carcinomas. Children with renal tumors (less than 18 years). Patients who are unfit for surgical treatment. Patients who are refusing surgical treatment.

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