3q26 Amplification is Rarely Present in Women Whose LSIL Cytology does not Represent CIN 2+ Disease

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionObjective: 10-17% of women with LSIL cytology truly have CIN 2+ disease at colposcopically directed biopsy and 20% of the CIN 2+ lesions derive from women with LSIL cytology. No molecular marker has yet been able to triage LSIL cytology effectively. If possible, the triage would spare women the referral to colposcopy. Irreversible chromosomal damage occurs during oncogenesis. Increasing cervical dysplastic severity occurs with increasing amplification of the 3q26 chromosomal region. The purpose of this study is to evaluate the test characteristics of 3q26 amplification in women whose routine cytology is reported as LSIL with emphasis on the negative predictive value for reassurance. Methods: We conducted a retrospective study using the available SurePath™ liquid cytology LSIL archival samples from women 17-59 years old which were linked to colposcopically directed biopsy samples taken on average 36 days after cytology sampling (3-90 day range). Nuclei from the LSIL samples were hybridized with a single-copy probe for the chromosome 3q26 region and a control probe for the centromeric alpha repeat sequence of chromosome 7, using standard FISH methods. Amplification was defined as five or more signals present in at least 2 cells. Results: Of the 68 paired cytology/biopsy samples, 3q26 amplification occurred in 40% of the women with CIN 2+ disease (sensitivity 95% CI: 12, 74). There was no amplification in 91% of women with less than CIN 2 disease (specificity 95% CI: 81, 97); and the negative predictive value was 90% (79, 96). Conclusions: The lack of 3q26 amplification in women with screening cytology LSIL results offers reassurance that CIN 2+ disease has not developed. Future prospective studies are ongoing

Lipid and Lipoprotein Profiles in Youth With and Without Type 1 Diabetes: The SEARCH for Diabetes in Youth Case-Control Study

OBJECTIVE—The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes

TAFII-independent activation mediated by human TBP in the presence of the positive cofactor PC4.

TFIID is a multiprotein complex comprised of the TATA-binding protein (TBP) and an array of TBP-associated factors (TAFIIs). Whereas TBP is sufficient for basal transcription in conjunction with other general transcription factors and RNA polymerase II, TAFIIs are additionally required for activator-dependent transcription in mammalian cell-free transcription systems. However, recent in vivo studies carried out in yeast suggest that TAFIIs are not globally required for activator function. The discrepancy between in vivo yeast studies and in vitro mammalian cell-free systems remains to be resolved. In this study, we describe a mammalian cell-free transcription system reconstituted with only recombinant proteins and epitope-tagged multiprotein complexes. Transcriptional activation can be recapitulated in this highly purified in vitro transcription system in the absence of TAFIIs. This TBP-mediated activation is not induced by human mediator, another transcriptional coactivator complex potentially implicated in activator response. In contrast, general transcription factors TFIIH and TFIIA play a significant role in TBP-mediated activation, which can be detected in vitro with Gal4 fusion proteins containing various transcriptional activation domains. Our data, therefore, suggest that TFIIH and TFIIA can mediate activator function in the absence of TAFIIs

Role of chromosome 3q26 gain in predicting progression of cervical dysplasia

Objective: This study aimed to determine whether 3q26 gain can predict which low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUSs) will progress to higher-grade squamous intraepithelial lesion (HSIL). Methods: Liquid cytology specimens of LSIL and ASCUS from 73 women were examined using fluorescent in situ hybridization (FISH) for the detection of 3q26 gain. All women underwent colposcopy and biopsy at the initial visit and 40 of them with histology showing cervical intraepithelial neoplasia 1 (CIN 1) or human papillomavirus infection (koilocytosis) were included in the study. They were reevaluated with liquid cytology, colposcopy, and biopsy after a median follow-up of 17.5 months. Results: A total of 40 cases were analyzed (31 LSILs and 9 ASCUSs). Of these cases, 8 (20%; 6 LSILs and 2 ASCUSs) were positive and 32 (80%) were negative for 3q26 gain according to FISH. Three of the 8 positive women (38%) progressed to HSIL/CIN 2 or worse, whereas none of the 32 negative women did so. 3q26 gain could predict progression with a negative predictive value of 100% (95% confidence interval, 89.1%Y100%). In addition, women positive for 3q26 gain had a significantly lower regression rate compared with negative women (P = 0.009). Conclusions: In this first prospective study, 3q26 gain in LSIL/ASCUS cytology exhibited an impressive negative predictive value for progression to HSIL/CIN 2 or worse. Thus, 3q26 gain may be useful in stratifying patients' risk for progression and possibly alter management and reduce cost of follow-up. © 2012 by IGCS and ESGO

Type 1 and Type 2 Diabetes in Asian and Pacific Islander U.S. Youth: The SEARCH for Diabetes in Youth Study

OBJECTIVE—Given limited reports on diabetes among U.S. Asian and Pacific Islander youth, we describe the clinical characteristics, incidence, and prevalence of diabetes among Asian, Pacific Islander, and mixed Asian–Pacific Islander youth