Z Takacs

Combination of p16 INK4a -Ki67 Immunocytology and HPV Polymerase Chain Reaction for the Noninvasive Analysis of HPV Involvement in Head and Neck Cancer

We recently read an interesting article by Linxweiler et al, who reported the use of p16-Ki67 immunocytochemistry combined with human papillomavirus (HPV) testing on cytological specimens for the assessment of HPV involvement in head and neck squamous cell carcinoma (HNSCC). Their findings regarding brush cytology and HPV testing are in agreement with the results of our previous study. In fact, we recently reported that abnormal brush cytology is strongly associated with a diagnosis of HNSCC and that HPV testing on cytobrushing specimens from patients with HNSCC is feasible and reliable. Linxweiler et al found a very high sensitivity (98%) and specificity (100%) for head and neck brush cytology, although the estimation of sensitivity based on an analytic population that was composed mostly of patients with cancer (50 of 65 patients) has to be regarded with caution. In fact, a recent work highlighted that disease prevalence affects test characteristics, including sensitivity. In addition, the high sensitivity reported by Linxweiler et al may depend on the fact that the samples were partly obtained during a panendoscopy, a procedure that guarantees a more thorough collection of cytological specimens compared with an ambulatory setting. Indeed, in an ambulatory setting, we collected 100 cytobrushing specimens from patients with HNSCC, and detected abnormal cells in only 77 of them (77%). Linxweiler et al also claimed that false-negative results regarding HPV status assessed on the cytological samples may be avoided by screening the samples for the presence of cancer cells prior to HPV testing. We performed the HPV test on 68 paired cytological-histological specimens from patients with HNSCC (Cohen kappa, 0.84) and based on our results, we only partly agree with the authors. In fact, among 9 morphologically negative cytobrushing specimens that corresponded to HPVpositive tumors, 3 specimens tested negative for HPV (thus representing false-negative results), whereas the other 6 were positive for HPV type 16, a finding that is in agreement with the respective tumor tissue. These findings demonstrate that cytological brushings may yield a reliable HPV test result despite the fact that they do not contain neoplastic cells. Although the performance of head and neck cytology can only be evaluated on a population-based sample, we believe that the study by Linxweiler et al represents a strong contribution toward promoting the use of brush cytology in patients with HNSCC for the assessment of HPV involvement in such tumors.

Combination of p16INK4a/Ki67 immunocytology and hpv polymerase chain reaction for the noninvasive analysis of HPV involvement in head and neck cancer: p16-Ki67 Dual Stain in HNSCC

High‐risk human papillomavirus (HPV) infection has been identified as a relevant risk for the development of head and neck squamous cell carcinomas (HNSCCs). As HPV status has also gained a role as a prognostic and predictive biomarker for this entity, there is a growing demand for valid HPV testing in HNSCC patients

The significance of anterolateral neck cysts in early diagnosis of fetal malformations.

The objective of this study is to examine the association of lateral fetal neck cysts with increased nuchal translucency, chromosomal abnormalities and fetal malformations.

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

BackgroundChromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology.MethodsExpression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers.ResultsFISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure.ConclusionsOur study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions.

Trial integration of combined ultrasound and laparoscopy tuition in an undergraduate anatomy class with volunteer participation — A pilot study

Anatomy is a cornerstone of medical undergraduate curricula. Due to increasing changes in various medical fields, a lot of new subjects were introduced in undergraduate curricula, while the teaching areas of basic sciences, i.e. anatomy, were reduced. The introduction of advanced diagnostic and therapeutic devices, i.e. ultrasound and laparoscopy, with outstanding imaging quality will be increasingly introduced in basic sciences. In our project, we examined the effect integrating ultrasound and laparoscopy in an anatomy undergraduate course to illustrate the female pelvis. Anatomy students that completed their practicum and cadaver dissection course were enrolled in our project. They received a theoretical introduction followed by a practical course of ultrasound or laparoscopy in the department of obstetrics and gynaecology. Following the course the students had to answer two questionnaires that evaluated their satisfaction, subjective knowledge-gain, problems and content of the course. At the end, a closing briefing was done to discuss the clinical skills and the course. The answers of the questionnaire were summed up in a Likert scale. 25 students were enrolled in the project. 52% attended laparoscopy operations, while 48% attended ultrasound examinations. After analysing the questionnaires using Likert scales (1=strongly agree, 5=strongly disagree) a general satisfaction of 1.5, a subjective knowledge gain of 2.4 and a thrive to extend these clinical skill programs in gynaecology and other specialities in basic science of 1.5 and 1.2, respectively, was reported. There were no statistically significant differences in the Likert scores between both groups (p>0.05). The introduction of ultrasound and laparoscopy in undergraduate basic science teaching programs is a promising method and should be further evaluated, standardized and expanded.

Einführung eines praktischen standardisierten Ultraschallkurses in der Medizinlehre

Hintergrund: Ultraschall ist ein zentrales Untersuchungsverfahren zur Erstellung medizinischer Diagnosen, zur Behandlung und zum Follow-up. Viele Fortschritte wurden mit Ultraschall vor allem im Bereich der pranatalen Medizin erreicht. Die Studenten haben durch ihre Lehrbucher allerdings nicht mehr als Illustrationen der Technik und ihrer Anwendungen erhalten. Ultraschalllehre fur Studenten wurde in letzter Zeit haufiger thematisiert, um die Qualitat der medizinischen Ausbildung fur Studenten zu verbessern. In unserer Arbeit untersuchten wir die Auswirkungen der Anwendung standardisierter Ultraschalllehre bei Studenten im Blockpraktikum. Methoden: Die Studenten haben wahrend ihres Blockpraktikums in der Gynakologie und Geburtshilfe einen theoretischen und praktischen Ultraschallkurs mit Hands-on erhalten. Die theoretischen und praktischen Kenntnisse wurden vor und nach dem Kurs mittels Mutliple-Choice-Fragen getestet. Nach dem Kurs wurden die Studenten aufgefordert, einen Evaluationsbogen auszufullen. Um das Lehrverfahren zu standardisieren, haben wir Peytons Vier-Stufen-Verfahren angewandt, das zum Erwerb von Ultraschallfahigkeiten eines DEGUM-Stufe-1-Untersuchers fur Frauenheilkunde erforderlich ist. Ergebnisse: Die Multiple-Choice-Noten vor und nach dem Kurs wiesen eine statistisch signifikante Verbesserung (p-Wert < 0,001) auf. Aus dem Evaluationsbogen ergab sich eine allgemeine Zufriedenheit der Studenten, subjektiv die Einschatzung einer Kompetenzerweiterung und die Forderung nach mehr sonographischem Hands-on im Gebiet der Geburtshilfe und Gynakologie sowie in anderen Bereichen der Medizin. Fazit: Praktische Ultraschalllehre bei Studenten im Blockpraktikum ist eine Methode mit zunehmenden Potential und sollte kunftig vermehrt evaluiert, standardisiert und ausgeweitet werden.