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Satelli A.,Texas Tech University Health Sciences Center | Rao P.S.,Texas Tech University Health Sciences Center | Thirumala S.,AmeriPath | Rao U.S.,Texas Tech University Health Sciences Center | Rao U.S.,1109 Amarillo Research Building
International Journal of Cancer

Development of colorectal cancer (CRC) involves a series of genetic alterations with altered expression of proteins and cell signaling pathways. Here, we identified that galectin-4 (gal-4), a marker of differentiation, was down-regulated in CRC. The goal of this work was to determine the function of gal-4 in CRC. Toward this goal, the human colon biopsies and tissue microarrays containing a gradient of pathology were analyzed for gal-4 expression by immunohistochemistry. Cell proliferation, migration, motility, forced expression, knockdown, cell cycle and apoptosis assays were used to characterize gal-4 function. Immunohistochemistry identified that gal-4 expression was significantly down-regulated in adenomas and was essentially absent in invasive carcinomas. Forced expression of gal-4 in gal-4 -ve cells induced cell cycle arrest and retarded cell migration and motility. Further, gal-4 sensitized the cells to camptothecin-induced apoptosis. Gal-4 knockdown resulted in increased cell proliferation, migration and motility. Gal-4 was found to be associated with Wnt signaling proteins. Finally, gal-4 expression led to down-regulation of Wnt signaling target genes. This study demonstrates that loss of gal-4 is a common and specific event in CRC. This study also shows that gal-4 exhibits tumor suppressive effects in CRC cells in vitro. Through its ability to interact with and down-regulate the functions of Wnt signaling pathway, gal-4 reveals a new dimension in the control of the Wnt signaling pathway. Thus, gal-4 may prove to be an important molecule in understanding the biology of CRC. Copyright © 2010 UICC. Source

Moriarty A.T.,AmeriPath | Nayar R.,Northwestern University | Arnold T.,Mid America Clinical Laboratories | Gearries L.,Mid America Clinical Laboratories | And 3 more authors.
Archives of Pathology and Laboratory Medicine

Context: Knowledge of human papillomavirus (HPV) status is expected to bias the morphologic evaluation of Papanicolaou (Pap) test results.Objective: To characterize Pap test result interpretive bias when the HPV status is known at the microscopic evaluation.Design: Forty HPV-positive liquid-based Pap test results initially interpreted as negative for squamous intraepithelial lesion or malignancy were selected from a quality assurance program, separated into 2 groups of 20 slides each and circulated in 2 groups to 22 members of the College of American Pathologists Cytopathology Committee. Each member reviewed each case and indicated whether the result was negative for squamous intraepithelial lesion or malignancy or was an epithelial cell abnormality (ECA). The participants assessed the severity of ECAs using the Bethesda System. The participants were not informed of the HPV status in the initial review round. Each group of 20 slides was then distributed to the opposite group (to avoid slide recall), and the participants were informed that all slides were from patients who were high-risk HPV positive. Differences in the responses between groups were analyzed by x2 test and Cochran-Mantel-Haenszel test at the .05 significance level.Results: Without knowledge of the HPV status, slides were more often categorized as negative for squamous intraepithelial lesion or malignancy and less likely identified as an ECA (P < .001). There was an increase across all categories of ECAs in the biased responses compared with the unbiased responses (P = .002).Conclusions: Knowledge of positive HPV status biases morphologic Pap test result interpretation. If the HPV status is positive, observers are more likely to report a Pap test result as abnormal across all categories of ECAs. Source

Clark K.L.,University of North Florida | Leydet B.F.,Louisiana State University | Threlkeld C.,AmeriPath
Journal of Medical Microbiology

The present study investigated the cause of illness in human patients primarily in the southern USA with suspected Lyme disease based on erythema migrans-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. The study also included some patients from other states throughout the USA. Several PCR assays specific for either members of the genus Borrelia or only for Lyme group Borrelia spp. (Borrelia burgdorferi sensu lato), and DNA sequence analysis, were used to identify Borrelia spp. DNA in blood and skin biopsy samples from human patients. B. burgdorferi sensu lato DNA was found in both blood and skin biopsy samples from patients residing in the southern states and elsewhere in the USA, but no evidence of DNA from other Borrelia spp. was detected. Based on phylogenetic analysis of partial flagellin (flaB) gene sequences, strains that clustered separately with B. burgdorferi sensu stricto, Borrelia americana or Borrelia andersonii were associated with Lyme disease-like signs and symptoms in patients from the southern states, as well as from some other areas of the country. Strains most similar to B. burgdorferi sensu stricto and B. americana were found most commonly and appeared to be widely distributed among patients residing throughout the USA. The study findings suggest that human cases of Lyme disease in the southern USA may be more common than previously recognized and may also be caused by more than one species of B. burgdorferi sensu lato. This study provides further evidence that B. burgdorferi sensu stricto is not the only species associated with signs and/or symptoms consistent with Lyme borreliosis in the USA. © 2014 The Authors Printed in Great Britain. Source

Fischer A.H.,University of Massachusetts Medical School | Clayton A.C.,Mayo Medical School | Bentz J.S.,Laboratory Medicine Consultants Ltd. | Wasserman P.G.,North Shore Long Island Jewish Health System | And 3 more authors.
Archives of Pathology and Laboratory Medicine

Context.-Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs). Objective.-To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Design.-Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hü rthle cell neoplasm), and malignant. For specific reference diagnoses of benign/ goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed. Results.-The 47 076 thyroid FNA slide responses, between 2001 and 2009, included 44 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, comparedwith 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p .001). Conclusions.-LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described. Source

Darragh T.M.,University of California at San Francisco | Winkler B.,Mount Kisco Medical Group | Souers R.J.,The American College | Laucirica R.,Baylor College of Medicine | And 2 more authors.
Archives of Pathology and Laboratory Medicine

Context.-Anal cytology is being used more frequently for anal cancer screening, yet many cytologists are unfamiliar with it. Objective.-To describe the performance of anal cytology in the College of American Pathologists' Interlaboratory Comparison Program in Non-Gynecologic Cytology (CAP NGC) educational slide program during a 6-year time span, from 2006 to 2011, using participant responses (pathologist, cytotechnologist, and laboratory). Design.-Concordance rates for the target diagnosis and general category for each slide challenge were analyzed. Four main factors were included in the analysis: (1) general category or specific responses, (2) program year from 2006 to 2011, (3) participant type (pathologist, cytotechnologist, or overall laboratory), and (4) preparation type (liquid-based or conventional). Results.-Participants most frequently correctly classified negative for intraepithelial lesion or malignancy, low lowgrade squamous intraepithelial lesion, and herpes simplex virus infection, with concordance rates of 78.8%, 85%, and 80.2%, respectively. Performance on challenges with target diagnoses of high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, and ameba was poor, with concordance rates of 57.1%, 56.2%, and 41.5%, respectively. Significant improvement during the 6 years was seen in the concordance rates of participants' responses for low-grade squamous intraepithelial lesion challenges but not for HSIL. There was no significant difference in performance by slide preparation type. Conclusions.- The poor performance on anal cytology in the CAP NGC program, especially with regard to correct identification of HSIL and squamous cell carcinoma, indicates that there is a need for continued education about anal cytology. Source

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