Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC will provide clues to treat this aggressive malignant tumor. Here, we report that the ubiquitin ligase praja2 forms a complex with-and ubiquitylates the AP2 adapter complex, contributing to receptor endocytosis and clearance. In human RCC tissues and cells, downregulation of praja2 by oncogenic miRNAs (oncomiRs) and the proteasome markedly impairs endocytosis and clearance of the epidermal growth factor receptor (EGFR), and amplifies downstream mitogenic and proliferative signaling. Restoring praja2 levels in RCC cells downregulates EGFR, rewires cancer cell metabolism and ultimately inhibits tumor cell growth and metastasis. Accordingly, genetic ablation of praja2 in mice upregulates RTKs (i.e. EGFR and VEGFR) and induces epithelial and vascular alterations in the kidney tissue.In summary, our findings identify a regulatory loop between oncomiRs and the ubiquitin proteasome system that finely controls RTKs endocytosis and clearance, positively impacting mitogenic signaling and kidney cancer growth.

Strategies and Controversies in the Treatment With Carbon Dioxide Laser of Laryngeal Hemangioma: A Case Series and Review of the Literature.

INTRODUCTION: The hemangioma is the most common vascular tumor, involving the head and neck in 60% of cases. It is rare in the larynx. In children, hemangiomas are more frequent on the subglottis, whereas in adults the most common site is the supraglottis. Laryngeal hemangioma with cavernous features isolated to the free edge of the vocal fold is a very rare clinical finding. We present 2 cases of glottic hemangioma. Both patients reported severe hoarseness. CASES: In the first patient, an extensive blue-purple mass was seen on the right vocal cord. The patient was posted for microlaryngeal surgery with carbon dioxide (CO2) laser. Second patient had a large, smooth, flesh-colored polypoid mass emanating from the left vocal cord. The patient was posted for microlaryngeal surgery. After 2 months, both patients showed a considerable voice improvement. DISCUSSION: Vocal cord hemangiomas are very rare, and they usually cause problem in the voice of the patient. A vascular lesion that may mimic a hemangioma may sometimes result from an organizing hematoma following a hemorrhage on the vocal cords due to voice abuse. Laryngeal hemangiomas also need to be distinguished pathologically from polypoidal vascular granulation tissue that may be produced by laryngeal biopsy, intubation, or trauma. Indirect endoscopy is enough to diagnosis. No active treatment is advised for adult laryngeal hemangiomas unless the lesions are symptomatic or show a tendency to involve other parts. There is no uniformly accepted treatment of head and neck hemangiomas. Surgical excision with laser CO2 microlaryngoscopic techniques gives satisfactory results.

Primary High-Grade Angiosarcoma of the Breast in a Young Woman With Breast Implants: A Rare Case and a Review of Literature.

Primary angiosarcoma (AS) of the breast is an extremely unusual variant of breast malignancies, and its incidence is about 0.05% of all primary breast tumors. In this article, we present a rare case of a primary AS that developed in a young woman with breast implants. This case report emphasizes importance of early investigation for accurate diagnosis and proper management of the breast AS, along with a correlation of histopathologic, radiologic, and clinical findings.

Immunophenotype of Atypical Polypoid Adenomyoma of the Uterus: Diagnostic Value and Insight on Pathogenesis.

Atypical polypoid adenomyoma (APA) is a rare uterine lesion constituted by atypical endometrioid glands, squamous morules, and myofibromatous stroma. We aimed to assess the immunophenotype of the 3 components of APA, with regard to its pathogenesis and its differential diagnosis. A systematic review was performed by searching electronic databases from their inception to January 2019 for immunohistochemical studies of APA. Thirteen studies with 145 APA cases were included. APA glands appeared analogous to atypical endometrial hyperplasia (endometrioid cytokeratins pattern, Ki67≤50%, common PTEN loss, and occasional mismatch repair deficiency); the prominent expression of hormone receptors and nuclear ß-catenin suggest that APA may be a precursor of "copy number-low," CTNNB1-mutant endometrial cancers. Morules appeared as a peculiar type of hyperdifferentiation (low KI67, nuclear ß-catenin+, CD10+, CDX2+, SATB2+, p63-, and p40-), analogous to morular metaplasia in other lesions and distinguishable immunohistochemically from both conventional squamous metaplasia and solid cancer growth. Stroma immunphenotype (low Ki67, α-smooth-muscle-actin+, h-caldesmon-, CD10-, or weak and patchy) suggested a derivation from a metaplasia of normal endometrial stroma. It was similar to that of nonatypical adenomyoma, and different from adenosarcoma (Ki67 increase and CD10+ in periglandular stroma) and myoinvasive endometrioid carcinoma (h-caldesmon+ in myometrium and periglandular fringe-like CD10 pattern).