Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma

<p>Abstract</p> <p>Background</p> <p>The SRY-related HMG-box family of transcription factors member <it>SOX2 </it>has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients.</p> <p>Methods</p> <p>Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for <it>SOX2</it>, <it>NANOG </it>and <it>OCT4 </it>gene expression by real-time PCR.</p> <p>Results</p> <p>SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432).</p> <p>Conclusions</p> <p>In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.</p

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC

Das ERG Rearrangement in kleinzelligen Prostata- und Lungenkarzinomen

Aims: Small cell prostate cancer is a rare but aggressive disease. Currently, its histogenetic origin is unclear and its distinction from metastatic small cell lung cancer is challenging. The aim of our study was to determine whether the ERG rearrangement commonly observed in acinar prostate cancer can distinguish small cell prostate cancer from small cell lung cancer samples. Methods and Results: We assessed 15 small cell prostate cancers and 22 small cell lung cancers for ERG rearrangement using FISH. Commonly used and novel immunohistochemical markers (i.e. AR, CANT1, GOLPH2, PSA, PSMA, CD56, EMA, TTF1, Chromogranin A, Synaptophysin and Ki-67) were further studied. ERG rearrangement occurs in 86% small cell prostate cancers but in none of the small cell lung cancers and is the best marker to differentiate between both tumours (p<0.0001). Conclusions: The ERG rearrangement is commonly observed in small cell prostate cancer supporting the hypothesis that ERG rearrangement occurs in aggressive prostate cancers. Furthermore, the ERG rearrangement is the most significant marker to differentiate between small cell prostate cancer and small cell lung cancer. Moreover, our data suggest that small cell prostate cancer is not a tumour entity on its own but a dedifferentiated variant of common acinar prostate cancer.Hintergrund: Das kleinzellige Prostatakarzinom ist eine seltene, aber sehr aggressive Erkrankung. Derzeit liegt der histogenetische Hintergrund dieser Neoplasie im Dunkeln und die Abgrenzung insbesondere von kleinzelligen Lungenkarzinomen ist oft schwierig. Ziel unserer Studie war es, zu untersuchen, ob das ERG Rearrangement, welches häufig in azinären Prostatakarzinomen beobachtet wird, dazu geeignet ist, zwischen kleinzelligen Lungenkarzinomen und kleinzelligen Prostatakarzinomen zu unterscheiden. Methoden und Ergebnisse: Wir untersuchten 15 kleinzellige Prostatakarzinome und 22 kleinzellige Lungenkarzinome mittels FISH auf ihren ERG Rearrangement Status. Darüber hinaus untersuchten wir die Gewebe auf bereits etablierte und neue immunhistochemische Marker (i.e. AR, CANT1, GOLPH2, PSA, PSMA, CD56, EMA, TTF1, Chromogranin A, Synaptophysin und Ki-67). Wir konnten ein ERG Rearrangement in 86% der kleinzelligen Prostatakarzinome, aber in keinem kleinzelligen Lungenkarzinom nachweisen. Damit ist ERG der beste Marker, um zwischen beiden Entitäten zu unterscheiden. Schlussfolgerung: Das ERG Rearrangement tritt häufig in kleinzelligen Prostatakarzinomen auf, was die Hypothese stützt, dass das ERG Rearrangement vorwiegend in aggressiven Verlaufsformen des Prostatakarzinoms auftritt. Darüber hinaus ist das ERG Rearrangement der signifikanteste Marker, um zwischen kleinzelligen Lungen- und Prostatakarzinomen zu unterscheiden. Unsere Daten weisen darauf hin, dass das kleinzellige Prostatakarzinom keine eigene Tumorentität ist, sondern eine dedifferenzierte Wuchsform des azinären Prostatakarzinoms

Implementing remote patient monitoring for patients during systemic cancer therapy

Mobile monitoring of outpatients during cancer therapy becomes possible through technological advancements. This study leveraged a new remote patient monitoring app for in-between systemic therapy sessions. Patients’ evaluation showed that the handling is feasible. Clinical implementation must consider an adaptive development cycle for reliable operations

Role of Rendezvous-Procedure in the Treatment of Complications after Laparoscopic Sleeve Gastrectomy

Introduction: Laparoscopic sleeve gastrectomy is one of the most commonly performed bariatric procedures worldwide with good results, high patient acceptance, and low complication rates. The most relevant perioperative complication is the staple line leak. For the treatment of this complication, endoscopic negative pressure therapy has proven particularly effective. The correct time to start endoscopic negative pressure therapy has not been the subject of studies to date. Methods: Twelve patients were included in this retrospective data analysis over three years. Endoscopic negative pressure therapy was carried out using innovative open pore suction devices. Patients were treated with simultaneous surgery and endoscopy, so called rendezvous-procedure (Group A) or solely endoscopically, or in sequence surgically and endoscopically (Group B). Therapy data of the procedures and outcome measures, including duration of therapy, therapy success, and change of treatment strategy, were collected and analysed. Results: In each group, six patients were treated (mean age 52.96 years, 4 males, 8 females). Poor initial clinical situation, time span of endoscopic negative pressure therapy (Group A 31 days vs. Group B 18 days), and mean length of hospital stay (Group A 39.5 days vs. Group B 20.17 days) were higher in patients with rendezvous procedures. One patient in Group B died during the observation time. Discussion: Rendezvous procedures for patients with staple line leaks after sleeve gastrectomy is indicated for serious ill patients with perigastric abscesses and in need of laparoscopic lavage. The one-stage complication management with the rendezvous procedure seems not to result in an obvious advantage in the further outcome in patients with staple line leaks after laparoscopic sleeve gastrectomy