Expression der Hormonrezeptoren sowie von PARP-1 in Desmoidfibromatosen

Einleitung: Aggressive Fibromatosen bzw. Desmoidtumoren sind gutartige, jedoch lokal invasive Tumoren. Aktuelle Therapiestandards beinhalten primär die radikale Exzision, wobei Resektionen in toto teilweise nur schwer zu erzielen sind. Inkomplette Resektionen führen oft zu Rezidivtumoren, welche nicht selten wiederholte Resektionen und adjuvante Radiotherapie erfordern. Hormonelle Therapien gelten teilweise als vielversprechend, bedürfen aber weiterer Evidenz. Das hier untersuchte DNA-Reparaturenzym Poly Adenosin Diphosphat Ribose Polymerase-1 (PARP-1) verfügt über therapeutisches Potential, wie bereits erste Therapierfolge mit PARP-Inhibition in anderen Entitäten, besonders Karzinomen und ausgewählten Sarkomen, erwiesen. Methodik: In dieser Studie, evaluierten wir retrospektiv die Expression von vier Hormonrezeptoren, Östrogenrezeptoren (ER) α und β (ESR1 und -2), Progesteronrezeptor (PR) sowie Androgenrezeptor (AR), als auch PARP-1, mittels Immunhistochemie und quantitativer RT-PCR in Gewebeproben ausgewählter Desmoidfibromatosen (n=69). Mittels Immunoreaktivitätsscore (IRS) determinierten wir die Färbereaktivität. Die Ergebnisse der PCR wurden numerisch als auch mit definierten Cutoffs analysiert. Die Expressionsmuster korrelierten wir hinsichtlich der Prognoserelevanz mit klinisch-pathologischen Parametern. Ergebnisse: Die analysierten Hormonrezeptoren zeigten nahezu keine Reaktivität in der Immunhistochemie. Einzig ER-β zeigt eine zytoplasmatische partiell positive Expression. PARP-1 zeigte variable nukleäre Positivität in allen gefärbten Proben mit IR-Werten von bis zu 6. Die RT-PCR zeigte signifikant höhere Expression von ESR2 (p=0,035) und AR (p=0,005) in mittelgroßen Tumoren (51-100 mm) verglichen mit kleineren Tumoren (< 51 mm). Primär- im Vergleich zu Rezidivtumoren zeigten stärkere AR-Expression in der RT-PCR (p=0,01). Dazu war die Expression des AR höher in intra- verglichen mit extraabdominellen Tumoren (p=0,01). Univariate Überlebensanalysen ergaben, dass höhere Expression von ESR1 mit kürzerem Gesamtüberleben verbunden ist (p=0,005). Multivariate Analysen zeigten, dass höhere PARP-1 Expression mit früheren Rezidiven assoziiert ist (p=0,003). Schlussfolgerung: Unsere Untersuchungen zeigen, dass eine höhere PARP-1-Expression in unserem Kollektiv mit einer schlechteren Prognose im Sinne eines verkürzten rezidivfreien Überlebens assoziiert ist. Die PARP-1 könnte daher ein interessantes Target einer neuen individualisierten Therapie sein. Der Hormonrezeptorstatus erscheint - nach den Ergebnissen unserer Arbeit - von geringer prognostischer Relevanz.Agressive Fibromatoses or desmoid tumors are benign, but locally invasive entities. State of the art therapy is mainly radical surgery, however incomplete resections are common. Incomplete surgery frequently results in recidive tumors, which request repeated resections and often adjuvant radiotherapy. Hormone modifying therapy needs further evidence, but seems to be promising. The investigated DNA repairing enzyme Poly Adenosine Diphosphate Ribose Polymerase-1 (PARP-1) might contain therapeutic potential, as shown in the successful treatment of several entities, e.g. selected carcinomas and sarcomas, by PARP-inhibition. Methods: In this study, we investigated the expression of four hormone receptors (estrogen receptors (ER) α and β (ESR1 and -2), progesterone receptor (PR), androgen receptor (AR)) as well as PARP-1 via immunohistochemistry and quantitative RT-PCR in tissue samples (n=69) of desmoid tumors. The results of the PCR were analysed numerically and with defined cutoffs. We determined the extent of immunohistochemical reactivity using the immunoreactivity score (IRS). Finally we correlated the expression patterns with clinical-pathologic parameters to determine prognostic factors. Results: The analysed hormone receptors showed almost no reactivity in immunohistochemistry. Solely ER-β showed partial cytoplasmic reactivity. PARP-1 revealed variable nuclear positivity with IRS ranging up to 6. PCR showed significantly higher expression of ER-β (p=0,035) and AR (p=0,005) in tumors with median tumor size (51-100 mm) compared to smaller tumors (< 51 mm). Primary tumors compared to relapse tumors showed stronger expression of AR in PCR (p=0,01). Moreover, expression of AR was higher in intra- compared to extraabdominal tumors (p=0,01). Univariate survival analysis showed higher expression of ER-α was associated with shorter survival (p=0,005). Multivariate analyses showed that higher PARP-1 expression was associated with earlier recurrence (p=0,003). Conclusion: According to this study PARP-1 expression is associated with poorer prognosis, i.e. faster recurrence. PARP-1 could be an interesting target for a personalized therapy. In this study the expression of hormone receptors was of minor prognostic relevance

Update on Histological Reporting Changes in Neuroendocrine Neoplasms.

PURPOSE OF REVIEW Classification and nomenclature of neuroendocrine neoplasms (NEN) have frequently changed over the last years. These changes reflect both increasing knowledge and international standardisation. RECENT FINDINGS The most recent changes in the Gastro-Entero-Pancreatic system induced the concept of well-differentiated NET with high proliferation rate (NET G3), explaining partially the heterogeneity of G3 NEN. Even if the nomenclature in pulmonary NEN is still different, the terms 'carcinoid' and 'atypical carcinoid' are widely overlapping with NET G1 and NET G2. Molecular data shows an additional heterogeneity both in well-differentiated NET and poorly differentiated NEC. However, no studies are available demonstrating clinical usefulness yet. The heterogeneity of NEN regarding the organ of origin, differentiation and molecular subtypes make development of personalised therapy a challenge needing more international and interdisciplinary collaborations and clinical trials allowing stratification according to biological subgroups

Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy.

BACKGROUND Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratified immunotherapy would interfere with cancer-specific cell surface receptors only. METHODS To identify such candidates, we profiled the surface receptors of the NCI-60 tumor cell panel via flow cytometry. The resulting surface receptor expression data were integrated into proteomic and transcriptomic NCI-60 datasets applying a sophisticated multiomics multiple co-inertia analysis (MCIA). This allowed us to identify surface profiles for skin, brain, colon, kidney, and bone marrow derived cell lines and cancer entity-specific cell surface receptor biomarkers for colon and renal cancer. RESULTS For colon cancer, identified biomarkers are CD15, CD104, CD324, CD326, CD49f, and for renal cancer, CD24, CD26, CD106 (VCAM1), EGFR, SSEA-3 (B3GALT5), SSEA-4 (TMCC1), TIM1 (HAVCR1), and TRA-1-60R (PODXL). Further data mining revealed that CD106 (VCAM1) in particular is a promising novel immunotherapeutic target for the treatment of renal cancer. CONCLUSION Altogether, our innovative multiomics analysis of the NCI-60 panel represents a highly valuable resource for uncovering surface receptors that could be further exploited for diagnostic and therapeutic purposes in the context of cancer immunotherapy

Value of an Action Cam in Surgical Pathology.

Grossing of surgical pathology specimens is a complex task, which may be challenging to master correctly. Despite the growing use of digital technology in other aspects of surgical pathology, little has been done so far to modernize the documentation of grossing. We used a portable video camera ("GoPro") to document different grossing procedures. The video material may be used for teaching purposes or might enhance the more commonplace macroscopic description by adding another dimension. Furthermore, video documentation may encourage the discussion of upcoming clinical questions or help rectify some possible initial impreciseness

Alien Registration- Bedford, George (Bar Harbor, Hancock County)

https://digitalmaine.com/alien_docs/19928/thumbnail.jp

[Mucous retention cyst of the alveolar bone radiologically mimicking a radicular cyst: A case presentation.]

One of the most frequent pathologies of jaw bone is a bacteria-induced inflammation at the apices of teeth with subsequent bone resorption that typically presents as a radiolucency in radiographs. Usually, corresponding clinical and radiographic findings correlate and allow for an accurate diagnosis. However, occasionally an unexpected and completely different diagnosis presents as documented in this case report. In a 55-year-old female patient, a radicular cyst was suspected in her right maxillary bone. The treatment plan included a cystectomy as well as apical surgery of the adjacent and root-canal filled teeth 15 and 16. However, the intraoperative finding absolutely did not fit a radicular cyst but rather a mucous retention cyst, as could be confirmed subsequently by histopathology. The diagnosis of a mucous retention cyst within the jaw bone is extraordinary and as such has never been described before in the literature