Dual-color, Break-apart FISH Assay on Paraffin-embedded Tissues as an Adjunct to Diagnosis of Xp11 Translocation Renal Cell Carcinoma and Alveolar Soft Part Sarcoma

Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 06/2010; 34(6):757-66. DOI: 10.1097/PAS.0b013e3181dd577e
Source: PubMed


Both Xp11.2 translocation renal cell carcinoma (RCC) and alveolar soft part sarcoma (ASPS) are characterized by various translocations disrupting chromosome Xp11.2, which result in gene fusions involving the TFE3 transcription factor gene. Diagnostic tools to detect translocations involving the TFE3 gene on chromosome X would be valuable in the evaluation of these tumors. We developed a dual-color, break-apart fluorescence in situ hybridization (FISH) assay to identify the chromosomal break point in paraffin-embedded tissue. This assay was validated using 4 cases of Xp11.2 RCC [proven by karyotype and/or reverse-transcriptase polymerase chain reaction (RT-PCR)], 2 cases of ASPS (proven by karyotype or RT-PCR), the UOK109 cell line carrying the inv(X) (p11;q12), and several negative controls (both neoplastic and non-neoplastic). This break-apart FISH assay is a relatively quick procedure for detecting Xp11.2 RCC and ASPS translocations and can be applied to archival paraffin-embedded tissue.

7 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.
    No preview · Article · Nov 2010 · Advances in anatomic pathology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50 mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3 years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.
    Full-text · Article · Dec 2010 · International Journal of Clinical Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, tPA potentiates impairment of pial artery dilation in response to hypotension after hypoxia/ischemia (H/I) in pigs. ATP and Ca sensitive K channels (Katp and Kca) are important regulators of cerebrovascular tone and mediate cerebrovasodilation in response to hypotension. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is upregulated after H/I, with the ERK isoform contributing to vasodilator impairment. This study examined the effect of H/I on Katp and Kca induced pial artery dilation and the roles of tPA and ERK during/after injury in piglets equipped with a closed cranial window. H/I blunted vasodilation induced by the Katp agonists cromakalim, calcitonin gene related peptide (CGRP) and the Kca agonist NS 1619; the effect of each was exacerbated by tPA. Pre- or post-injury treatment with EEIIMD, a hexapeptide derived from plasminogen activator-1, and ERK antagonist U 0126 prevented Katp and Kca channel agonist induced vasodilator impairment while the inactive analogue EEIIMR had no effect. ERK was upregulated after H/I, which was potentiated by tPA. These data indicate that H/I impairs K channel mediated cerebrovasodilation. tPA augments loss of K channel function after injury by upregulating ERK. These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by impairing cation-mediated control of cerebrovascular tone.
    Full-text · Article · Feb 2011 · Brain research
Show more