Publications

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Our pathologists are actively engaged in cancer-related research and publishing. To date, PhenoPath pathologists have authored more than 400 scientific articles and publications. Over 100 of those publications reflect research conducted at PhenoPath.

Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) Gene Status in Human Breast Cancer

Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) Gene Status in Human Breast Cancer Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens by Fluorescence In Situ Hybridization (FISH)

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Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH

Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens

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Markers of metastatic carcinoma of breast origin

This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained.

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Vascular mesangial channels in human nodular diabetic glomerulopathy

The presence of vascular mesangial channels has been reported in idiopathic nodular glomerulosclerosis and diabetic glomerulopathy. However, only limited information on the morphology and immunohistochemical phenotype of these channels is available.

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Practical Applications in Immunohistochemistry: Carcinomas of Unknown Primary Site

Context .- Identification of the site of origin of carcinoma of unknown primary using immunohistochemistry is a frequent requirement of anatomic pathologists. Diagnostic accuracy is crucial, particularly in the current era of targeted therapies and smaller sample sizes.

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Comparative Sensitivities and Specificities of Antibodies to Breast Markers GCDFP-15, Mammaglobin A

Comparative Sensitivities and Specificities of Antibodies to Breast Markers GCDFP-15, Mammaglobin A, and Different Clones of Antibodies to GATA-3: A Study of 338 Tumors Using Whole Sections

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Personalized oncogenomics: clinical experience with malignant peritoneal mesothelioma

Personalized oncogenomics: clinical experience with malignant peritoneal mesothelioma using whole genome sequencing

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BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations

A variety of immunohistochemical (IHC) stains have been proposed to mark either benign or malignant mesothelial proliferations. Loss of the p16 tumor suppressor (CDKN2A), through homozygous deletions of 9p21, is a good marker of mesotheliomas but lacks sensitivity.

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The lung-restricted marker napsin A is highly expressed in clear cell carcinomas of the ovary

OBJECTIVES: We recently observed expression of the "lung" marker napsin A in ovarian clear cell carcinomas and therefore sought to determine the extent of napsin A expression in a subset of ovarian neoplasms.

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GATA-3 expression in trophoblastic tissues

GATA-3 expression in trophoblastic tissues: an immunohistochemical study of 445 cases, including diagnostic utility.

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IMP3 and GLUT-1 Immunohistochemistry for Distinguishing Benign From Malignant Mesothelial Proliferations

Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial.

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Immunohistochemistry as an adjunct in the differential diagnosis of radiation-induced atypia versus urothelial carcinoma in situ of the bladder

Muscle invasive urothelial carcinoma has been treated with cystectomy ± adjuvant therapy. Recently, a bladder-sparing protocol has been offered to selected patients closely followed with surveillance biopsies. In this setting, radiation-induced changes (RAD-Ch) may be very difficult to distinguish from carcinoma in situ, and failing to recognize them may lead to overtreatment.

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Flow cytometric principles in hematopathology.

Dr. Kussick authored the chapter "Flow Cytometric Principles in Hematopathology" in Hematopathology, 2nd Edition, ed. by E. Hsi, series ed. J.R. Goldblum. Philadelphia, PA, Saunders, Elsevier, Chapter 23, 2012. This chapter is divided into five major sections.

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Concordance between human epidermal growth factor receptor 2 testing by reverse transcriptase polymerase chain reaction and fluorescent in situ hybridization.

Dabbs et al1 reported a study of human epidermal growth factor receptor 2 (HER2) status in a series of patients with breast cancer, comparing results via fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR), the latter employing the Oncotype DX assay (Genomic Health, Redwood City, CA).

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Comparison of clot-based vs. chromogenic factor Xa procoagulant phospholipid activity assays.

We compared 2 commercial plasma procoagulant phospholipid activity (PPA) assays, chromogenic, using bound annexin V to capture phosphatidylserine-containing microparticles, and clot-based. In both, anionic phospholipids accelerated activation of prothrombin by factor Xa. PPA levels were lower in the chromogenic vs the clot-based assay, with poor correlation between methods:

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Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma:  clinicopathologic analysis of 52 cases of rare aggressive subtypes of renal cell carcinoma with a focus on their interrelationship.

Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma are rare aggressive neoplasms of putative distal nephron origin. First described in 1949, case reports and review articles constitute a major source of information on collecting duct carcinoma, whereas Davis and colleagues and the pediatric tumor registry have contributed the seminal works on renal medullary carcinoma. Here we present a detailed study of collecting duct carcinoma (n=39) and renal medullary carcinoma (n=13), characterizing these rare neoplasms and analyzing their interrelationship.

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Guidelines for Pathologic Diagnosis of Malignant Mesothelioma:  2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

Context.-Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective.-To provide updated practical guidelines for the pathologic diagnosis of MM. Data Sources.-Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks.

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Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen.

Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

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Pulmonary hyalinizing granuloma with associated elevation in serum and tissue IgG4 occurring in a patient with a history of sarcoidosis.

This case provides the first definitive evidence that PHG is part of the spectrum of IgG4-related sclerosing disease.

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Routine pathologic parameters can predict Oncotype DX recurrence scores in subsets of ER positive patients: who does not always need testing?

When cost and time are a consideration and the added value of Oncotype DX® testing is in question, it may be reasonable to assume the results of this test in two specific subsets of breast cancers: (1) grade 1, high PR, low Ki67 cancers (low RS), and (2) grade 3, low PR, high Ki67 cancers (high RS).

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Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy.

Additional FISH studies that use probes to the SMS, RARA and TP53 genes are an effective way to determine the true HER2 amplification status in patients with polysomy 17, and they have important potential implications for guiding HER2-targeted therapy in breast cancer.

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The knowns and the unknowns in HER2 testing in breast cancer

The 2007 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for HER2 immunohistochemical and fluorescence in situ hybridization (FISH) testing in breast cancer address the potential impact of several “knowns” (eg, effect of fixative composition and fixation time).1,2 However, data continue to be generated that shed further light on the impact of “unknowns,” ie, selected preanalytic, analytic, and postanalytic (ie, interpretive) factors, on HER2 immunohistochemical testing.

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Immunophenotyping of thyroid tumors identifies molecular markers altered during transformation of differentiated into anaplastic carcinoma.

The markers observed to change during thyroid cancer progression validate prior observations and represent promising molecular diagnostic or prognostic tools and identify targets for therapy of ATC.

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Best practices in diagnostic immunohistochemistry: myoepithelial markers in breast pathology.

To demonstrate the presence or absence of myoepithelial cells, a panel-based approach of 2 or more markers is recommended.

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Effect of Xpcl1 activation and p27 (Kip1) loss on gene expression in murine lymphoma PLoS One 11: 6(3): e14758

Mice lacking the p27(Kip1) Cdk inhibitor (Cdkn1b) exhibit increased susceptibility to lymphomas from the Maloney murine leukemia virus (M-MuLV), and exhibit a high frequency of viral integrations at Xpcl1 (Kis2), a locus on the X-chromosome. Xpcl1 encodes miR-106a~363, a cluster of microRNAs that are expressed in response to adjacent retroviral integrations.

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Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification.

Our data of a large series with uniform definitional criteria confirm the malignant potential for pure epithelioid PEComas and provide adverse prognostic parameters for risk stratification in these patients.

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Thyroid transcription factor-1 expression in breast carcinomas.

We conclude that a small proportion of breast carcinomas show TTF-1 expression. Therefore, the presence of TTF-1 immunoreactivity in a carcinoma cannot by itself be used to exclude the possibility of a breast origin.

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Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples.

We present an algorithm for the stepwise application of p63, TTF1, CK5/6, CK7, Napsin A, and mucicarmine in situations in which separation of ADC from SCC in small specimens cannot be accomplished by morphology alone.

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Human epidermal growth factor receptor 2 assessment in a case-control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories.

There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.

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Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients.

We observed substantial treatment response in patients lacking three postulated predictors that would be difficult to attribute to cyclophosphamide alone. Patients who are HER2 negative and lack TOP2A amplification and PS17 should not be excluded from receiving DOX-containing regimens.

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Diagnostic utility of galectin-3 in thyroid cancer.

The development of Gal-3 as a diagnostic marker for thyroid cancer represents a promising avenue for future study, and its clinical application could significantly reduce the number of diagnostic thyroid operations performed for cases of indeterminant fine needle aspiration biopsy cytology, and thus positively impact the current management of thyroid nodular disease.

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Fibrillins in human adult ovary and polycystic ovary syndrome: is fibrillin-3 affected in PCOS?

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age.

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