Publications (43) View all
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Article: Selective immunohistochemical markers to distinguish between metastatic high-grade urothelial carcinoma and primary poorly differentiated invasive squamous cell carcinoma of the lung.
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ABSTRACT: Context.-Distinction between primary lung carcinomas and metastases from other sites, especially the urinary tract, is a common diagnostic dilemma. As urothelial carcinomas can demonstrate a broad range of morphology and frequently demonstrate squamous differentiation, discerning metastatic urothelial carcinoma to the lung from primary pulmonary squamous cell carcinoma can be challenging. Objective.-To investigate immunostains that may aid in the distinction of urothelial carcinoma metastatic to the lung. Design.-Staining patterns of 14 markers in primary urothelial carcinoma of the bladder and primary squamous cell carcinoma of the lung were examined to establish a diagnostic panel. These antibodies were subsequently tested on tumors taken from 30 patients with a paired urinary tract and metastatic lung lesion. Results.-The best markers to distinguish poorly differentiated metastatic urothelial carcinoma from primary pulmonary squamous cell carcinoma were CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III, with the utility of the latter dependent upon the quantity of tissue available for analysis. The observed percentage positive staining in nonmetastatic urothelial carcinoma versus primary pulmonary squamous cell carcinoma with these antibodies was as follows: CK7 (100% versus 33%), CK20 (54% versus 7%), GATA-3 (78% versus 23%), CK14 (32% versus 77%), desmoglein-3 (11% versus 87%), and uroplakin III (14% versus 0%). Similar expression patterns were observed among the paired cases. Conclusion.-When interpreted in correlation with clinical history and histomorphology, a panel of immunostains including CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III may be a useful adjunct in the distinction of metastatic urothelial carcinoma to the lung.Archives of pathology & laboratory medicine 11/2012; 136(11):1339-46. · 2.58 Impact Factor -
Article: Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the antitumor activity of mammalian sterile 20-like kinase 1.
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ABSTRACT: Mst1/Stk4, a hippo-like serine-threonine kinase, is implicated in many cancers, including prostate cancer. However, the mechanisms regulating Mst1 remain obscure. Here, we characterized the effects of phospho-Thr-120 on Mst1 in prostate cancer cells. We demonstrated that phospho-Thr-120 did not alter the nuclear localization or cleavage of Mst1 in a LNCaP or castration-resistant C4-2 prostate tumor cell model, as revealed by a mutagenesis approach. Phospho-Thr-120 appeared to be specific to cancer cells and predominantly localized in the nucleus. In contrast, phospho-Thr-183, a critical regulator of Mst1 cell death, was exclusively found in the cytoplasm. As assessed by immunohistochemistry, a similar distribution of phospho-Mst1-Thr-120/Thr-183 was also observed in a prostate cancer specimen. In addition, the blockade of PI3K signaling by a small molecule inhibitor, LY294002, increased cytoplasmic phospho-Mst1-Thr-183 without having a significant effect on nuclear phospho-Mst1-Thr-120. However, the attenuation of mammalian target of rapamycin (mTOR) activity by a selective pharmacologic inhibitor, Ku0063794 or CCI-779, caused the up-regulation of nuclear phospho-Mst1-Thr-120 without affecting cytoplasmic phospho-Mst1-Thr-183. This suggests that PI3K and mTOR pathway signaling differentially regulate phospho-Mst1-Thr-120/Thr-183. Moreover, mutagenesis and RNAi data revealed that phospho-Thr-120 resulted in C4-2 cell resistance to mTOR inhibition and reduced the Mst1 suppression of cell growth and androgen receptor-driven gene expression. Collectively, these findings indicate that phospho-Thr-120 leads to the loss of Mst1 functions, supporting cancer cell growth and survival.Journal of Biological Chemistry 05/2012; 287(28):23698-709. · 4.77 Impact Factor -
Article: Case of fulminant giant-cell myocarditis associated with polymyositis, treated with a biventricular assist device and subsequent heart transplantation.
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ABSTRACT: Giant-cell myocarditis is an autoimmune myocarditis that rapidly progresses to heart failure, and is often associated ventricular tachycardia. We describe an otherwise healthy patient who was acutely ill with decompensated heart failure and ventricular tachycardia associated with rash and polymyositis, who then developed cardiogenic shock and multiorgan failure due to giant-cell myocarditis.Heart & lung: the journal of critical care 03/2011; 40(4):340-5. · 1.04 Impact Factor -
Article: Oncocytoma of the kidney with prominent intracytoplasmic lumina.
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ABSTRACT: Oncocytoma is a histologically distinctive neoplasm of the kidney, with a well-recognized cytoarchitectural appearance. On occasion, however, renal oncocytomas are known to exhibit unusual morphologic features that may pose diagnostic difficulties. We present the clinical and pathologic details of an oncocytoma of the kidney with an unusual histologic appearance imparted by the presence of large numbers of prominent intracytoplasmic lumens. Morphologically, the neoplasm was composed of uniform polygonal cells with copious amounts of granular, eosinophilic cytoplasm, round nuclei, and prominent nucleoli, exhibiting an organoid pattern of growth. Intracytoplasmic lumina of varying size were present throughout the tumor. There were no mitotic figures or areas of necrosis present. The diagnosis of oncocytoma was supported by immunohistochemical and ultrastructural studies. By electron microscopy, the intracytoplasmic lumens appeared as membrane bound spaces with associated microvilli. The presence of intracytoplasmic lumina in a significant proportion of cells is an uncommon feature of renal oncocytoma which can generate problems in diagnosis. Awareness of this phenomenon should allow for improved recognition of oncocytomas exhibiting this type of unusual morphology.Annals of diagnostic pathology 01/2011; 15(6):485-9. -
Article: Congenital mesoblastic nephroma.
The Journal of urology 03/2010; 183(3):1188-9. · 4.02 Impact Factor
