Ricardo V Lloyd

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (516)1912.43 Total impact

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    ABSTRACT: Some thyroid nodules such as follicular adenomas (FAs), follicular variant of papillary thyroid carcinomas (FVPTCs), and follicular thyroid carcinomas (FTCs) exhibit similar clinical presentations and gross morphologic appearances. The differential diagnosis of these lesions is sometimes difficult based on morphologic, cytologic, or clinical features alone. miR-146b-5p and miR-21 deregulation has been associated with progression and metastasis of thyroid cancers. However, the utility of in situ hybridization (ISH) to determine the cellular localization, diagnostic, and prognostic significance of miR-146b-5p and miR-21 expression in thyroid tumors has not been extensively analyzed. In order to examine the expression of miR-146b-5p and miR-21 in benign and malignant thyroid tissues and to determine if these microRNAs could be assigned to distinct histomorphological types of thyroid nodules, we analyzed miR-146b-5p and miR-21 expression in thyroid nodules on tissue microarrays (TMAs) with 193 thyroid specimens by ISH. miR-146b-5p and miR-21 expression in thyroid tissues was also analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). miR-146b-5p was highly expressed (89 %) in papillary thyroid carcinomas (PTCs) and 41 % of FVPTC. The expression of miR-146b-5p was not expressed in most FTCs, anaplastic thyroid carcinomas (ATCs), poorly differentiated thyroid carcinomas (PDTCs), or FAs (7, 8, 0, and 0 %, respectively). MiR-21 was overexpressed in 83 % of ATCs, 79 % of PTCs, 34 % of FVPTCs, and 19 % of PDTCs. The expression of miR-21 was not expressed in most FAs (9 %) or FTCs (4 %). Normal thyroid tissues and most benign goiters were negative for miR-146b-5p and miR-21. qRT-PCR analysis supported the ISH findings. PTC cases with positive expression of miR-146b-5p and miR-21 had significantly poorer disease-free survival rates. Immunohistochemical staining for HBME-1 showed positive staining in PTCs (100 %) and FVPTCs (92 %) with a subset of FTC (40 %) staining positive, while all FAs were negative. Since miR-146b-5p was mainly expressed in PTC including FVPTC and was not expressed in most FTC, PDTC, or ATC, it may serve as a useful diagnostic marker for PTC. ISH is a useful method to analyze microRNA expression in formalin-fixed paraffin-embedded thyroid tissues.
    Endocrine Pathology 03/2015; DOI:10.1007/s12022-015-9363-x · 1.64 Impact Factor
  • Jason Nathaniel Rosenbaum, Ricardo V. Lloyd
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    ABSTRACT: Pancreatic neuroendocrine neoplasms (Pan-NENs) are rare but clinically important lesions. Pan-NENs are known for and often categorized by their capacity to produce clinical syndromes mediated by the production of hormones. Despite sometimes presenting dramatically from excessive hormone production, not all Pan-NENs produce functional hormone, and they can pose diagnostic challenges to practicing pathologists. Distinguishing Pan-NENs from mimics can be crucial, because Pan-NENs carry different prognoses and have unique treatments available due to their specific biological properties. This article reviews the current categorization and features of Pan-NENs.
    Surgical Pathology Clinics 12/2014; 7:559–575.
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    ABSTRACT: The diagnosis of malignant thyroid tumors in some cytologic and histologic specimens remains challenging. High-mobility group A2 (HMGA2) expression and insulin-like growth factor II mRNA-binding protein-3 (IMP3) expression were evaluated by relative quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The aim of this study was to evaluate whether the combination of HMGA2 and IMP3 qRT-PCR was diagnostically useful in differentiating benign from malignant thyroid neoplasms. Fine-needle aspiration (FNA) specimens from 120 patients including 56 benign lesions and 64 carcinomas were used. The available 80 corresponding formalin-fixed paraffin-embedded (FFPE) thyroid tissues from 66 patients were also included in this study. HMGA2 and IMP3 expression levels were detected by qRT-PCR and reported as relative fold change after normalizing with a calibrator. The diagnostic utilities of HMGA2 and IMP3 qRT-PCR tests were evaluated individually and in combination. In FNA specimens, HMGA2 and IMP3 expression was consistently higher in thyroid malignancies compared with benign lesions in all subgroups except in Hürthle cell tumors. After exclusion of Hürthle cell tumors, the sensitivity was 90.2% for HMGA2, 88.2% for IMP3, and 98% for HMGA2+IMP3; the specificity was 97.1% for HMGA2, 79.4% for IMP3, and 79.4% for HMGA+IMP3. qRT-PCR data showed similar results in FFPE tissues: the sensitivity was 84.2% for HMGA2, 85.7% for IMP3, and 94.7% for HMGA2+IMP3; the specificity was 96.9% for HMGA2, 91.2% for IMP3, and 90.6% for HMGA2+IMP3. qRT-PCR data were concordant between FNA and FFPE samples for HMGA2 (97.4%) and IMP3 (96.9%). The results indicate that HMGA2 qRT-PCR with high specificity may be a useful ancillary technique to assist in the classification of difficult thyroid specimens, excluding Hürthle cell tumors. The HMGA2 and IMP3 qRT-PCR combination model with increased sensitivity and negative predictive value (96.4%) may be useful in screening thyroid cytology specimens.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 10/2014; 23(1). DOI:10.1097/PAI.0000000000000031 · 2.06 Impact Factor
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    ABSTRACT: Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future.
    The Oncologist 09/2014; 19(11). DOI:10.1634/theoncologist.2014-0182 · 4.54 Impact Factor
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    ABSTRACT: Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC. This was a retrospective review of adult (a parts per thousand yen18) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p < 0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease-specific mortality (DSM). Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM; 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.2-3.0, p < 0.01) and multifocality (OR 3.0, 95% CI 2.5-3.6, p < 0.01) were the strongest predictors of LNM. Importantly, LNM did not independently predict DSM (p = 0.52). Tumor size > 4 cm (hazards ratio [HR] 5.3, 95% CI 2.2-12.8, p < 0.01) and extrathyroidal extension (HR 8.2, 95% CI 3.0-22.0, p < 0.01) were the strongest predictors of DSM. LNM occur in less than 10% of patients with FVPTC but do not impact DSM. Instead, DSM in FVPTC is related to size and local invasion.
    Annals of Surgical Oncology 08/2014; 22(1). DOI:10.1245/s10434-014-3964-3 · 3.94 Impact Factor
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    ABSTRACT: Histological and cytological criteria in predicting clinical outcomes in patients with oncocytic poorly differentiated carcinoma (PDC) of the thyroid were investigated. In a set of 102 PDC patients, we performed a computer-assisted evaluation of cell size based on two different methods. Univariate analysis showed that cell size was a discriminant prognostic parameter in oncocytic PDC (30 cases) but not in the non-oncocytic carcinomas cases (72 cases). Patients with oncocytic PDC with small medium cell size had a significantly increased risk of death (p=0.029) and a decrease of disease-free survival (p=0.014). This correlation was absented in cases of non-oncocytic PTC, where age and extensive vascular invasion were significant indicators of progression. The proposed morphological signature shows a robust discriminatory ability when tested on the oncocytic PDC group and cell size assessment could thus be proposed as an inexpensive and readily evaluable parameter for predicting prognosis and planning therapy in this tumor type.
    Human pathology 07/2014; 45(7). DOI:10.1016/j.humpath.2014.02.027 · 2.81 Impact Factor
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    ABSTRACT: Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRX-1; alias PRRX1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-β1-induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-β1-induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression.
    American Journal Of Pathology 06/2014; 184(8). DOI:10.1016/j.ajpath.2014.04.011 · 4.60 Impact Factor
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    Ricardo V. Lloyd, Zhenying Guo, Heather Hardin
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    ABSTRACT: Thyroid cancer is one of the most rapidly increasing malignancies. The reasons for this increase is not completely known, but increases in the diagnosis of papillary thyroid microcarcinomas and follicular variant of papillary thyroid carcinomas along with the enhanced detection of well differentiated thyroid carcinomas are probably all contributing factors. Although most cases of well differentiated thyroid carcinomas are associated with an excellent prognosis, a small percentage of patients with well differentiated thyroid carcinomas as well as most patients with poorly differentiated and anaplastic thyroid carcinomas have recurrent and/or metastatic disease that is often fatal. The cancer stem cell model suggests that a small number of cells within a cancer, known as cancer stem-like cells, are responsible for resistance to chemotherapy and radiation therapy, as well as for recurrent and metastatic disease.. In this review we will focus on current studies about thyroid cancer stem-like cells, the processes of epithelial to mesenchymal transition, and mesenchymal to epithelial transition that provide plasticity to cancer stem-like cell growth in addition to the role of microRNAs in cancer stem cell development and regulation. Understanding the biology of cancer stem cells, epithelial to mesenchymal transition and the metastatic cascade should lead to the design of more rational targeted therapies for highly aggressive and fatal thyroid cancers.
    Endocrine Related Cancer 04/2014; 21(5). DOI:10.1530/ERC-14-0002 · 4.91 Impact Factor
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    ABSTRACT: Pituitary lactotrophs secrete prolactin. This process is enhanced by estrogen and inhibited by dopamine. Prolactinomas are benign neoplasms that rarely increase in size and are classified according to size as microadenomas (10 mm diameter). The clinical features of prolactinomas most commonly result from prolactin’s effect on the gonads and breast in women and from mass effect in men. This review details the clinical features and management of patients with prolactinomas.
    Expert Review of Endocrinology &amp Metabolism 01/2014; 7(2). DOI:10.1586/eem.12.4
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    ABSTRACT: Recent reports indicate that hobnail papillary thyroid carcinoma (HPTC) is a rare, but very aggressive variant of papillary thyroid carcinoma. The authors describe the cytological features of five HPTC on fine-needle aspiration biopsies (FNAB). Moreover, their immunophenotype and the presence of B-RAF mutation by pyrosequencing were investigated. The patients' (three females and two males) age ranged from 27 to 86 (mean 65) years. Tumor size ranged from 2 to 9 cm (mean 4.2 cm). FNAB were highly cellular with a bloody background and scant colloid. The cells were arranged in papillary-like clusters or in micropapillary groups. The cell population consisted of medium-sized cells with "tear-drop" cytoplasm, apically placed nuclei that produced a surface bulge leading to a hobnail appearance. At higher magnification, nuclei showed variable degrees of atypia, occasional pink intranuclear pseudoinclusions, and grooves. Nuclear stratification and atypical mitotic figures were usually present. Immunocytochemistry revealed positive staining for thyroglobulin, thyroid transcriptor factor-1, Hector Battifora Mesothelial Antigen-1, partial loss of E-cadherin expression, and nuclear expression of p53 protein. B-RAF mutation was present in three out of five cytological cases. Immunohistochemical and molecular results were confirmed on histological sections. Recognizing the unique cytological features of HPTC should help to avoid misdiagnosis of this rare variant. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 01/2014; 42(1). DOI:10.1002/dc.23028 · 1.52 Impact Factor
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    ABSTRACT: Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (n = 32), follicular thyroid carcinomas (n = 28), and papillary thyroid carcinomas (n = 57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n = 10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90 % of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1, and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p < 0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well-differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression.
    Endocrine Pathology 10/2013; 24(4). DOI:10.1007/s12022-013-9272-9 · 1.64 Impact Factor
  • Ricardo V Lloyd
    Human pathology 08/2013; 44(8):1455-6. DOI:10.1016/j.humpath.2013.05.002 · 2.81 Impact Factor
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    ABSTRACT: Extra-appendiceal colonic carcinoids are uncommon neuroendocrine tumors with a poor prognosis compared with carcinoids of other gastrointestinal origins. Few studies have examined the clinicopathologic profile and behavior of this rare tumor. A retrospective analysis was performed on patients with colonic carcinoid tumors evaluated at a single tertiary care center between 1996 and 2012. Collected data included patient and tumor characteristics, presentation, treatment, recurrence, and survival. Results were integrated into a comprehensive review of the colonic carcinoid literature. In total, 114 patients with colorectal carcinoid tumors were identified, and 15 patients with extra-appendiceal tumors were analyzed. The mean age was 58.6 ± 3.0 y, and subjects were predominantly male (73.3%). The most common presenting problem was abdominal pain (33.3%), although 26.7% of patients were asymptomatic. Cecal tumors were the most prevalent (73.3%), and most patients underwent right hemicolectomy. Three patients with lesions < 1 cm were treated endoscopically. The mean tumor diameter was 2.9 ± 0.5 cm, with lymph node or distant metastasis present in 53.3% and 26.7%, respectively. All but two patients underwent a presumed curative resection. During a mean follow-up of 4.2 ± 1.0 y, there was only one death (non-carcinoid specific). Eleven patients were alive without evidence of disease at last follow-up and three patients were alive with disease, one of whom initially had a presumed curative resection that recurred. This case series further elucidates the clinicopathologic characteristics of colonic carcinoid tumors, which aids physicians in guiding the diagnosis and management of these rare tumors.
    Journal of Surgical Research 06/2013; DOI:10.1016/j.jss.2013.05.107 · 2.12 Impact Factor
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    ABSTRACT: Cancer stem-like cells are a subpopulation of self-renewing stem cells in cancers that are more resistant to chemotherapy and radiation therapy. Evidence supporting the existence of cancer stem-like cells in thyroid and in many other solid tissue cancers is rapidly accumulating. These cells have been studied using specific biomarkers such as CD133, CD44, and aldehyde dehydrogenase enzymes. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in nonadherent culture (ultra-low attachment plates) or in extracellular matrix leading to cell spheres formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice often results in rapid growth of xenografts, which express cancer stem-like cell biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines including papillary, follicular, medullary, and anaplastic carcinoma cell lines. They have also been identified in primary thyroid cancers and have been shown to have similar properties as the cancer stem-like cells in thyroid cancer cell lines. Immunohistochemical staining with CD133 and other biomarkers has been used to characterize thyroid cancer stem-like cells in paraffin sections of thyroid cancers. Recent studies of epithelial-mesenchymal transition in which cells lose their epithelial features and acquire mesenchymal phenotypes have shown that these changes are present in thyroid cancers. Biomarkers used to characterize epithelial-mesenchymal transition have also been studied in primary thyroid cancers. A close relationship between epithelial-mesenchymal transition and stem cell features of cancers has been identified in recent studies. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal thyroid cancers.
    Human pathology 03/2013; 44(9). DOI:10.1016/j.humpath.2013.01.009 · 2.81 Impact Factor
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    ABSTRACT: Cancer stem-like cells are a subpopulation of self-renewing cells that are more resistant to chemotherapy and radiation therapy than the other surrounding cancer cells. The cancer stem cell model predicts that only a subset of cancer cells possess the ability to self-renew and produce progenitor cells that can reconstitute and sustain tumor growth. Evidence supporting the existence of cancer stem-like cells in the thyroid, pituitary, and in other endocrine tissues is rapidly accumulating. These cells have been studied using specific biomarkers including: CD133, CD44, Nestin, Nanog, and aldehyde dehydrogenase enzyme. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in low attachment plates or in extracellular matrix leading to sphere formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice results in growth of xenografts which express cancer stem-like biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines, in primary thyroid cancers, in normal pituitary, and in pituitary tumors. Other recent studies suggest the existence of stem cells and cancer stem-like cells in endocrine tumors of the gastrointestinal tract, pancreas, lungs, adrenal, parathyroid, and skin. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal endocrine cancers.
    Endocrine Pathology 02/2013; 24(1). DOI:10.1007/s12022-013-9235-1 · 1.64 Impact Factor
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    ABSTRACT: The pituitary is the master endocrine gland of the body. It undergoes many changes after birth, and these changes may be mediated by the differentiation of pituitary stem cells. Stem cells in any tissue source must display (1) pluripotent capacity, (2) capacity for indefinite self-renewal, and (3) a lack of specialization. Unlike neural stem cells identified in the hippocampus and subventricular zone, pituitary stem cells are not associated with one specific cell type. There are many major candidates that are thought to be potential pituitary stem cell sources. This article reviews the evidence for each of the major cell types and discuss the implications of identifying a definitive pituitary stem cell type.
    Pituitary 02/2013; DOI:10.1007/s11102-013-0470-8 · 2.22 Impact Factor
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    ABSTRACT: Islet-1 (Isl1) is a transcription factor involved in the embryogenesis of islets of Langerhans. Immunohistochemically, Isl1 is a sensitive lineage-specific marker for pancreatic neuroendocrine neoplasms (NENs) and their metastases. Its specificity has not been documented, nor have large numbers of NENs from other parts of the gut or other organs been studied. We examined Isl1 expression in 203 primary NENs (gastroenteropancreatic, lung, breast, and ovarian neoplasms) and 40 hepatic NEN metastases (enteropancreatic and lung neoplasms) from known primaries. The correlation between Isl1 and CDX2 expression was studied using a tissue microarray containing 46 pancreatic NENs. Immunostaining for Isl1 and CDX2 was also performed in selected NENs from other sites. Isl1 was positive in 90% of pancreatic, 89% of duodenal, 100% of rectal, 38% of colonic, 14% of appendiceal, and 6% of ileal primaries. Isl1 was negative in all other NENs. Among metastatic neoplasms, 76% of pancreatic and 2 of 2 rectal NEN metastases were Isl1 positive, whereas all other tested metastases were negative. The overall sensitivity and specificity of Isl1 in identifying primary pancreatic NENs was 88% and 80%, respectively. Thirty-six of 46 pancreatic NENs in the tissue microarray were Isl1 positive; 4 were Isl1 negative but CDX2 positive. Our findings confirm that Isl1 is a sensitive marker of pancreatic origin in cases of metastatic NEN. However, Isl1 does not distinguish pancreatic NEN from duodenal and colorectal NEN, even when used in association with CDX2.
    The American journal of surgical pathology 01/2013; 37(3). DOI:10.1097/PAS.0b013e31826f042c · 4.59 Impact Factor
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    ABSTRACT: Well-differentiated small intestinal neuroendocrine tumors are rare malignancies. They arise from enterochromaffin cells and very little is known about differential microRNA (miRNA) expression. The aim of this study was to identify the miRNA profile of well-differentiated small intestinal neuroendocrine tumors, which may have a critical role in tumor development, progression and potentially develop miRNAs as novel clinical biomarkers. Specimens from two test groups, 24 small intestinal neuroendocrine tumor specimens at different stages of malignancy, are included in this study. Total RNA from the first test group, five primary tumors, five mesentery metastases and five liver metastases was hybridized onto the Affymetrix Genechip miRNA arrays to perform a genome-wide profile. The results were validated by using quantitative real-time PCR (QRT-PCR) and northern blot analyses. We then expanded the investigation to laser capture microdissected small intestinal neuroendocrine tumor cells and immuno-laser capture microdissected normal enterochromaffin cells of the first test group. Furthermore, a second test group, three primary tumors, three mesentery metastases and three liver metastases, was included in the study. Thus, two independent test groups validated the data by QRT-PCR. Moreover, we characterized nine miRNAs, five (miR-96, -182, -183, -196a and -200a), which are upregulated during tumor progression, whereas four (miR-31, -129-5p, -133a and -215) are downregulated. Several online software programs were used to predict potential miRNA target genes to map a number of putative target genes for the aberrantly regulated miRNAs, through an advanced and novel bioinformatics analysis. Our findings provide information about pivotal miRNAs, which may lead to further insights into tumorigenesis, progression mechanisms and novel therapeutic targets recognition.Modern Pathology advance online publication, 18 January 2013; doi:10.1038/modpathol.2012.216.
    Modern Pathology 01/2013; 26(5). DOI:10.1038/modpathol.2012.216 · 6.36 Impact Factor
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    ABSTRACT: Pituitary tumor-transforming gene (PTTG1) has been implicated in several oncogenic processes. The aim of this study was to determine PTTG expression in brain tumors. We investigated 88 benign and malignant brain tumors. PTTG immunoexpression was evaluated using a scale of 0 to 3. PTTG immunoexpression was nuclear and cytoplasmic in most tumors, except for medulloblastomas and hemangiopericytomas. Expression was highest in medulloblastomas. Higher grade gliomas including glioblastoma multiforme (GBM) IV and astrocytoma III had the highest level of PTTG expression, whereas low-grade gliomas had the lowest levels of PTTG expression. Hemangiopericytomas had the lowest levels of PTTG immunoreactivity, with meningiomas and schwannomas exhibiting similarly low PTTG levels. Nuclear PTTG immunoreactivity was higher than cytoplasmic in higher-grade tumors. Our results indicate that PTTG immunoexpression is higher in aggressive brain tumors including medulloblastomas, GBM IV, and astrocytoma III, whereas in more benign tumors, PTTG immunoexpression is lower.
    Anticancer research 01/2013; 33(1):119-22. · 1.87 Impact Factor
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    ABSTRACT: Background The necessity and frequency of post-operative surveillance for appendiceal carcinoid tumors ≤1 cm is undetermined. Methods A retrospective review of all patients with appendiceal carcinoid tumors ≤1 cm managed at an academic, tertiary referral center. Clinicopathologic characteristics, treatment, surveillance, recurrence, and survival were assessed and analyzed. Results Over a 16-year period, 31 patients met inclusion criteria. Appendicitis (n=17) and pelvic mass (n=5) were the most common presentations. Median tumor diameter was 5 mm (range=1-10 mm). Two patients had mesoappendiceal involvement. No patients had regional lymph node involvement or distant metastasis. Post-operatively, 14 patients (45%) received follow-up recommendations, including one or more of the following: imaging (n=9), medical oncology referral (n=7), colonoscopy (n=5), or laboratory studies (n=5). There were no recurrences or disease-specific deaths during a median follow-up period of 5 years (range=0-15 years). Conclusions Appendiceal carcinoids ≤1 cm are unlikely to recur. Therefore, post-operative surveillance may be unnecessary.
    American journal of surgery 01/2013; 207(3). DOI:10.1016/j.amjsurg.2013.08.038 · 2.41 Impact Factor

Publication Stats

14k Citations
1,912.43 Total Impact Points

Institutions

  • 2010–2014
    • University of Wisconsin–Madison
      • Department of Pathology and Laboratory Medicine
      Madison, Wisconsin, United States
    • Università degli Studi di Torino
      • Department of Medical Science
      Torino, Piedmont, Italy
  • 1993–2013
    • Mayo Clinic - Rochester
      • • Department of Laboratory Medicine & Pathology
      • • Department of Internal Medicine
      Рочестер, Minnesota, United States
  • 2011
    • University of California, San Francisco
      • Department of Pathology
      San Francisco, CA, United States
  • 1989–2011
    • University of Toronto
      • • Laboratory Medicine Program
      • • Division of Anatomy
      • • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 2009
    • Queen's University
      • Department of Pathology and Molecular Medicine
      Kingston, Ontario, Canada
  • 2001–2008
    • University of Santiago de Compostela
      • Department of Anatomy and Animal Production
      Santiago, Galicia, Spain
    • University of Cincinnati
      • Department of Pathology and Laboratory Medicine
      Cincinnati, OH, United States
  • 2006
    • Toho University
      Edo, Tōkyō, Japan
  • 2004
    • Gulhane Military Medical Academy
      • Department of Pathology
      Ankara, Ankara, Turkey
  • 2003
    • Teikyo University
      Edo, Tōkyō, Japan
  • 2002–2003
    • St. Jude Children's Research Hospital
      • Department of Pathology
      Memphis, Tennessee, United States
    • Wakayama Medical University
      Wakayama, Wakayama, Japan
  • 2000
    • Tokai University
      Hiratuka, Kanagawa, Japan
    • Kitasato University
      Edo, Tōkyō, Japan
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 1997
    • Nippon Medical School
      • Department of Neurosurgery
      Tokyo, Tokyo-to, Japan
  • 1982–1995
    • University of Michigan
      • • Department of Human Genetics
      • • Department of Pathology
      • • Department of Internal Medicine
      Ann Arbor, Michigan, United States
  • 1983–1994
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1992
    • Stanford University
      • Division of Abdominal Transplantation
      Palo Alto, CA, United States
  • 1987
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, Michigan, United States
  • 1986
    • University of Michigan-Dearborn
      • Department of Natural Sciences
      Dearborn, Michigan, United States
    • Vanderbilt University
      Nashville, Michigan, United States