Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin

Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.

Immunohistochemical Expression of Wnt-4 Protein in Clear Cell Renal Carcinoma

Wingless binding integration site proteins (Wnt) have an important role in normal kidney development and in various kidney diseases. They are required for complete epithelial differentiation and normal nephron formation. Changes in these proteins could also have important role in carcinogenesis. This study included 185 patients with clear cell renal carcinoma (ccRCC) in whom immunohistochemical expression of Wnt-4 protein in healthy and tumorous tissue after surgery was investigated. There was higher expression of Wnt-4 in healthy than in tumor tissue. No difference between Fuhrman’s grade and Wnt-4 expression was found. A poor negative correlation between tumor size and Wnt-4 expression was found. Patients with suspected metastatic diseases had higher Wnt-4 expression. There was no difference in survival rates between Wnt-4 negative and positive groups. In our study we have shown that high Wnt-4 expression in healthy tissue decreases in low-grade tumors but then increases in high-grade tumors, suggesting that tumor progression requires Wnt-4 activation or reactivation.

Metastatic Clear Cell Renal Carcinoma with Benign Ultrasonographic Findings in the Thyroid Gland

Metastasis to the thyroid gland is rare, and the incidence of thyroid metastasis is from 1.4% to 3% for all thyroid malignancies. The most common metastatic malignancy to the thyroid gland is renal cell carcinoma. Ultrasonography is useful to assess the malignancy risk of thyroid nodules, and the ultrasonographic features of metastatic renal cell carcinoma in the thyroid gland are hypoechoic solid nodules with increased vascularity. Here, we report a case of metastatic clear cell renal carcinoma with benign ultrasonographic features and fine-needle aspiration cytology in the thyroid gland. A 76-year-old woman visited our hospital for surgical management of a growing left thyroid mass. Her history comprised previous left nephrectomy for an unknown reason. Thyroid ultrasonography revealed a well-defined, isoechoic, solid mass. Left thyroidectomy was performed, and the final diagnosis was metastatic clear cell renal carcinoma of the thyroid gland.

Antiangiogenic Therapy in Clear Cell Renal Carcinoma (CCRC): Pharmacological Basis and Clinical Results

Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, many tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, pazopanib, axitinib, and cabozantinib), one monoclonal antibody (bevacizumab), and two mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus) have been investigated and approved for the treatment of advanced or metastatic clear cell renal carcinoma (metastatic CCRC) in first-line, as well as second-line, therapy, with impressive results in progression-free survival and in the objective response rate compared with previously available therapies or placebo. Recently, a new type of drug has been approved for metastatic CCRC: immunomodulatory checkpoint inhibitors (ICIs), alone or in combination with TKIs. However, many questions and areas to be explored still remain with regard to clear cell renal carcinoma (CCRC) treatment: research on predictive biomarkers, the best patient selection, how to overcome the mechanisms of resistance, and the best sequence of therapies in daily clinical practice. This review focuses on the pharmacological properties and anticancer activities of these drugs. The toxicity profile and clinical limitations of these therapies are also discussed.

piRNA-31115 Promotes Cell Proliferation and Invasion via PI3K/AKT Pathway in Clear Cell Renal Carcinoma

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that play important roles in germline development and carcinogenesis. In this study, we used the deep sequencing of small RNA Transcriptome to explore the piRNA expression in six clear cell renal carcinoma (ccRCC) tissues and matched adjacent normal tissues and found that six piRNAs were upregulated and sixteen were downregulated in ccRCC tissues. Among them, piRNA-31115 (NCBI accession number: DQ571003) was the most upregulated piRNA in ccRCC tissues compared with matched adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to confirm piR-31115 expression in other ccRCC tissues ( n = 40 ) and ccRCC cell lines. Besides, function analysis demonstrated that silencing of piR-31115 inhibited ccRCC cell proliferation, motility, and invasiveness. Mechanistic investigations showed that piRNA-31115 may activate epithelial-mesenchymal transition (EMT) via the PI3K/AKT signaling pathway. Hence, piR-31115 may represent an oncogene in the development of ccRCC.

Solitary Choroid Plexus Metastasis of Clear Cell Renal Carcinoma 11years after nephrectomy : A case report

Brain metastasis are the most commun intracranial tumours amongst adults. While brain metastasis of Renal cell carcinoma (RCC) are less commun, intraventricular localisation is particularly rare. There are few small series and mostly case reports which have noted intraventricular involvement of RCC metastasis. Here we report a new case of Solitary choroid plexus metastasis of clear cell renal carcinoma 11 years after nephrectomy.It’s about a 51-year-old patient, diagnosed with renal tumor in 2010 and a nephrectomy was performed. He presented with a frontal syndrome consecutive to a left frontal intraventricular tumor with ipsilateral ventricular dilation. He was operated on for a complete excision of this tumor. Histopathological examinations revealed a metastasis of clear cell renal carcinoma. He underwent 3 radiosurgery sessions one month later. At 6 months of follow-up, he has described an important clinical improvement, mainly of his frontal syndrome.BM secondary to RCC tend to be located in the ventricular system with close association to the choroid plexus. Early detection of brain metastases, and a therapeutic strategy including surgery and radiosurgery can offer patients an extended survival.