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Saul Suster

Bio: Saul Suster is an academic researcher from Medical College of Wisconsin. The author has contributed to research in topics: Thymic carcinoma & Carcinoma. The author has an hindex of 66, co-authored 470 publications receiving 18256 citations. Previous affiliations of Saul Suster include University of Alabama at Birmingham & University of Alabama.


Papers
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Journal ArticleDOI
TL;DR: It is concluded that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.
Abstract: Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the up-regulation (11- to 19-fold) of miR-221, -222, and -146 was strongest showed dramatic loss of KIT transcript and Kit protein. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.

1,243 citations

Journal ArticleDOI
01 Aug 2010-Pancreas
TL;DR: Issues in the pathologic assessment of NETs that are common among primaries of different sites are examined and the distinction of well-differentiated from poorly differentiated NETs and the significance of proliferative rate in prognostic assessment are examined.
Abstract: Neuroendocrine tumors (NETs) arise in most organs of the body and share many common pathologic features. However, a variety of different organ-specific systems have been developed for nomenclature, grading, and staging of NETs, causing much confusion. This review examines issues in the pathologic assessment of NETs that are common among primaries of different sites. The various systems of nomenclature are compared along with new proposal for grading and staging NETs. Although differences persist, there are many common themes, such as the distinction of well-differentiated (low and intermediate-grade) from poorly differentiated (high-grade) NETs and the significance of prolif- erative rate in prognostic assessment. A recently published minimum pathology data set is presented to help standardize the information in pathology reports. Although an ultimate goal of standardizing the pathologic classification of all NETs, irrespective of primary site, remains elusive, an understanding of the common themes among the different current systems will permit easier translation of information relevant to prognosis and treatment.

1,014 citations

Journal ArticleDOI
15 Feb 1991-Cancer
TL;DR: The morphologic features of the tumors in patients with thymic carcinoma correlated well with their clinical behavior; histologic type constituted the most reliable and important predictor of prognosis.
Abstract: The clinicopathologic features of 60 patients with thymic carcinoma were studied. Patients ranged in age from 10 to 76 years (mean, 46), of whom 24 were females and 36 were males. Overall survival at 1, 3, and 5 years was 56.6%, 40%, and 33.3%, respectively. The following morphologic features were correlated with survival: type of tumor margins; presence or absence of a lobular growth pattern; nuclear atypia; necrosis; mitotic activity; and histologic tumor type and grade. Eighty eight percent of patients with poorly circumscribed/infiltrating neoplasms died of their tumors as compared with 16.6% of patients with well-circumscribed neoplasms (P less than 0.0000). Of patients whose tumors had mitotic counts exceeding 10/10 high-power fields (HPF), 84.3% died, as compared with 21.4% of patients with lower mitotic counts (P less than 0.0000). Of patients whose tumors showed lack of lobular growth pattern, 91.6% died, as compared with 29% of those whose tumors had a lobular growth pattern (P less than 0.0000). Finally, 84.6% of patients whose tumors displayed a high-grade histology (lymphoepithelioma-like carcinoma, small cell/neuroendocrine carcinoma, clear cell carcinoma, sarcomatid carcinoma, and anaplastic/undifferentiated carcinoma) died of tumor, as compared with 0% of patients whose tumors were of low-grade histology (well-differentiated squamous carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma) (P less than 0.0000). Evaluation of the various treatment modalities used to treat these patients did not yield any statistically significant correlations with survival. Two clinically distinct groups of patients were identified: one after a relatively favorable clinical course with long survival, and one after a rapidly fatal outcome. The morphologic features of the tumors in these patients correlated well with their clinical behavior; histologic type (and the grade to which it was assigned) constituted the most reliable and important predictor of prognosis.

458 citations

Journal ArticleDOI
TL;DR: It is reported that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines and has potential therapeutic application against lung cancers.

347 citations

Journal ArticleDOI
TL;DR: The frequent CK20 positivity observed in salivary gland small cell carcinomas in this series suggests that at least some of them may be more closely related biologically to Merkel cell carcinoma than to pulmonary-type smallcell carcinoma, which may explain why they are far less clinically aggressive than other small cell cancers.
Abstract: Cytokeratin 20 (CK20) is a low-molecular-weight cytokeratin (CK) that shows restricted expression in the gastrointestinal epithelium, urothelium, and Merkel cell. Recent studies have suggested that since Merkel cell (primary cutaneous neuroendocrine) carcinomas are consistently CK20-positive, this feature may help to distinguish it from pulmonary small cell carcinomas. However, only limited numbers of these tumors have been studied, and the pattern of CK20 expression in other small cell carcinomas has not been established. Therefore, we studied CK20 expression in small cell carcinomas from a wide variety of sites. Immunohistochemical study was performed on paraffin sections using CK20 antibody, coupled with antigen retrieval by pressure cooking in citrate buffer. The cases included 34 Merkel cell carcinomas and 89 small cell carcinomas from various sites (pulmonary, 37; gastrointestinal tract, nine; pharynx and tongue, two; sinonasal tract, three; salivary gland, five; larynx, nine; breast, two; thymus, three; uterine cervix and corpus, 12, prostate, three; urinary bladder, two; kidney, one; pancreas, one). In addition, all cases were immunostained with pan-CK (MNF-116) and low-molecular-weight CK (CAM5.2) antibodies to ascertain their epithelial nature. With the exception of one case, all Merkel cell carcinomas were CK20-positive; and 30 of the 33 cases showed a punctate pattern. Almost 100% of tumor cells were positive, except for two cases that showed staining of 10% and 30% of tumor cells, respectively. Among the other small cell carcinomas, only five cases were CK20-positive, including one of 37 pulmonary (40% cells positive in punctate pattern), one of 11 cervical (10% cells positive), and three of five salivary gland (100% cells positive). We conclude that CK20-positivity in a small cell carcinoma of uncertain origin strongly predicts a diagnosis of Merkel cell carcinoma, especially if the majority of tumor cells are positive. A negative CK20 reaction can practically rule out Merkel cell carcinoma, provided that an effective antigen retrieval technique is used and appropriate staining is obtained with other cytokeratin antibodies. The frequent CK20 positivity observed in salivary gland small cell carcinomas in this series suggests that at least some of them may be more closely related biologically to Merkel cell carcinoma than to pulmonary-type small cell carcinoma. This may explain why they are far less clinically aggressive than other small cell carcinomas.

339 citations


Cited by
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Journal ArticleDOI
TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Abstract: MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

6,345 citations

Journal Article
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Abstract: MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

6,306 citations

Journal Article
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Abstract: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.

6,064 citations

Journal ArticleDOI
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
Abstract: MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer

5,693 citations