Publications by authors named "Theresa L Pasha"

Germ-cell tumors (GCTs) are the most common malignancies in adolescent and young men. These tumors are highly treatable, even at an advanced stage; therefore, accurate diagnosis is imperative. In this study, we evaluated immunohistochemical stains for SALL4, NANOG, glypican-3 (GPC3), D2-40, and CD30 with adequate control in retroperitoneal dissection specimens under the same laboratory conditions.

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Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1.

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Objective: To determine whether connexin (Cx) expression is altered in cervical dysplasia.

Study Design: Cx proteins form gap junctions and are expressed in squamous epithelia including ectocervix. We used multispectral imaging to perform a quantitative immunohistochemical survey of Cx43 Cx26 in 37 archival human cervical specimens.

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The DNA-binding factor TFE3 is closely related to microphthalmia-associated transcription factor (MiTF) and is over-expressed in alveolar soft part sarcoma (ASPS) and select renal cell carcinomas. Reports of TFE3 expression in PEComa prompted investigation into TFE3 expression among other members of the putative MiTF group of neoplasms. The authors examined cases of PEComa (n = 6), conventional angiomyolipoma (AML; n = 22), metastatic melanoma (n = 16), and clear cell sarcoma (CCS; n = 9) for TFE3 expression.

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Hypoxia is known to play important role in cancer biology.  In sarcomas, hypoxia-induced protein biomarkers such as Hypoxia Inducible Factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), and Erythropoietin (Epo) have been previously reported in only a few studies.  Moreover, the biologic significance and relationship to tumorigenesis of these hypoxia-induced biomarkers is not well understood in the context of sarcoma.

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Background & Aims: Recurrent hepatitis C with ensuing fibrosis is the leading cause of liver allograft loss. We investigated whether histologic features in early posttransplant liver biopsies could predict the rate of fibrosis progression in this population.

Methods: From 1999 to 2007 there were 476 liver transplants performed for hepatitis C at our center.

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Thyroid transcription factor-1 (TTF-1) is a 38-kd nuclear protein, and a member of the NKx2 family of homeodomain transcription factors. It is highly expressed in normal and neoplastic thyroid and lung tissues, and is considered a reliable marker for lung adenocarcinoma and thyroid carcinoma. Recently, expression of TTF-1 has also been reported in ovarian, endometrial, and endocervical epithelial neoplasms.

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Thyroid transcription factor-1 (TTF-1) is a 38-kd homeodomain containing DNA-binding protein, identified in thyroid and lung as a regulator of thyroid-specific genes and surfactant and Clara cell secretory protein gene expression. TTF-1 has been used as a reliable lineage marker for lung adenocarcinoma and thyroid carcinoma in surgical pathology. However, TTF-1 expression has been recently reported in carcinomas of other origins including female genital tract.

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The immaturity of teratomas is usually manifested as immature neuroepithelium. The amount of immature neuroepithelium has been correlated with the survival of adult patients with ovarian immature teratoma. To date, no immunohistochemical marker has been found to facilitate the identification of immature teratoma.

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The Wilms tumor 1 (WT-1) is a zinc finger transcription factor essential for the development of the kidneys and gonads. Alterations in the WT-1 gene were observed in several tumor types. Depending on the tumor types, WT-1 might function as a tumor suppressor or as a survival factor.

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CD43, a sialoglycoprotein expressed on hematopoietic cells, has only rarely been reported in nonhematopoietic tumors, mostly of colon. We describe CD43 expression by immunohistochemistry and mRNA in situ hybridization in adenoid cystic carcinomas (ACCs). CD43 immunoreactivity with 2 different antibodies was detected mainly in ACC but also 1 membranous type basal cell adenocarcinoma and 1 colonic adenocarcinoma.

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Cancer/testis (CT) antigens are named after their expression pattern as they are typically present in various types of tumors and in the germ cells of normal adult testis. Adult ovarian tissue is usually reported to be CT antigen negative. Based on the differences in female versus male gonadal development, the ovarian counterpart of the most predominant CT antigen positive testicular germ cells are not prevalent in the adult ovary.

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To evaluate and compare the immunophenotype of endocervical and endometrial stromal cells and to asses its potential application in tumor localization. Paraffin sections of benign endocervix (n = 24), benign endometrium (n = 33), endocervical adenocarcinoma (n = 9), endometrial carcinoma (n = 13), and endometrial hyperplasia (n = 16) were stained with antibodies to CD10, Wilms Tumor-1, CD34, smooth muscle actin, and factor XIIIa by immunohistochemistry. In 16 cases, lower uterine segment was also available.

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Chordomas and low-grade chondrosarcomas of the central nervous system share many histological features, generating, at times, considerable diagnostic difficulty and, not infrequently, requiring immunohistochemical analysis for appropriate classification. While both chordomas and chondrosarcomas stain positively for S100, only chordomas typically express epithelial antigens like cytokeratins and epithelial membrane antigen. Positive or negative staining with these latter two markers currently represents the only immunohistochemical technique that effectively distinguishes chordomas from chondrosarcomas.

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Background: The p63 and p73 genes are members of the p53 family and play an important role in stem cell identity and cellular differentiation and are expressed in basal and myoepithelial cells. In this study, we examined the expression of p63 and p73 in 50 various benign salivary gland lesions and 45 malignant salivary gland tumors.

Methods: The 95 salivary gland tumors were selected from the archives of the Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania.

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Histologically, desmoplastic small round cell tumor is composed of the characteristic neoplastic small round cells with divergent differentiation, and distinct desmoplastic stroma. Genetically, the tumor shows a characteristic 11;22 translocation, involving the EWS gene on chromosome 22 and the WT1gene on chromosome 11 to produce an EWS-WT1 fusion gene which generates a chimeric protein functioning as a novel transcription factor that activates expression of target genes such as PDGF-A. Expression of PDGF-A, a potent growth factor for fibroblasts, has been detected in desmoplastic small round cell tumors and has been linked to the characteristic desmoplasia in these tumors.

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Although immunohistochemistry has proven to be valuable in the differentiation of epithelioid mesothelioma from pulmonary or metastatic adenocarcinoma, no single antibody has demonstrated absolute sensitivity or specificity in making this distinction. Using immunohistochemical analysis with D2-40, a recently available monoclonal antibody that has been used as a lymphatic endothelial marker, we examined 53 cases of mesothelioma, 28 cases of reactive pleura, 30 cases of pulmonary adenocarcinoma, 35 cases of renal cell carcinoma, 26 cases of ovarian serous carcinoma, 16 cases of invasive breast carcinoma, 11 cases of prostatic adenocarcinoma, and seven cases of urothelial carcinoma. In addition, immunohistochemistry using calretinin, cytokeratin 5/6, and WT1 was performed on all cases of mesothelioma, pulmonary adenocarcinoma, ovarian serous carcinoma, and renal cell carcinoma.

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To determine its usefulness as a specific diagnostic marker for follicular carcinomas (FCs) vs other follicular-patterned thyroid lesions and possible application to fine-needle aspiration specimens, we immunohistochemically studied peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in histologic sections (FC, 13 cases; follicular adenoma [FA], 11; follicular variant of papillary carcinoma [FVPC], 9) and surrounding thyroid tissue by using a PPAR gamma monoclonal antibody. Positivity (detected by nuclear staining) was scored as absent, weak, moderate, or strong. When only moderate or strong nuclear staining was considered positive, 9 FCs (69%), 3 FAs (27%), and 2 FVPCs (22%) demonstrated positive nuclear immunoreactivity.

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Human papillomavirus (HPV) is recognized as a causal agent for cervical carcinomas. Assimilation of HPV oncogenes E6 and E7 into the host DNA promotes upregulation of cyclin dependent kinase inhibitor (CDKI) p16(INK4A), detectable by monoclonal antibody in the developing cervical cancer cells. The aim of this study was to 1) develop a protocol for p16(INK4A) immunocytochemical staining on SurePath preparations, and 2) determine its utility as an HPV marker on a spectrum of cervical reactive and neoplastic lesions.

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Context: The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions.

Design: We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas.

Results: Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma.

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