Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update

Periostin, also called osteoblast-specific factor 2, is a secreted cell adhesion protein, which shares a homology with the insect cell adhesion molecule fasciclin I. It has been shown to be an important regulator of bone and tooth formation and maintenance, and of cardiac development and healing. Recent studies revealed that periostin plays an important role in tumor development and is upregulated in a wide variety of cancers such as colon, pancreatic, ovarian, breast, head and neck, thyroid, and gastric cancer as well as in neuroblastoma. Periostin binding to the integrins activates the Akt/PKB- and FAK-mediated signaling pathways which lead to increased cell survival, angiogenesis, invasion, metastasis, and importantly, epithelial-mesenchymal transition of carcinoma cells. In this review we summarize recent clinicopathological studies that have investigated periostin expression in lung, kidney, prostate, liver cancer, and malignant pleural mesothelioma and discuss the role of periostin isoforms in tumorigenesis and their potential as targets for stroma-targeted anticancer therap

The pros and comms of gene sequencing

Full-gene sequencing undoubtedly comes with its pluses and its minuses. In this article, the authors aim to weigh up the pros and cons not only from the point of view of the patient but also in view of the doctor's possible perspective. Either party may be for or against it for a variety of reasons - for example, a fear of knowing too much on the part of the patient, and concerns about possible over-treatment on the part of the healthcare professional. One thing is certain: the possibility of full-gene sequencing is here and here to stay. At the very least, doctors need to make patients aware of their options, while offering balanced advice

Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update

Periostin, also called osteoblast-specific factor 2, is a secreted cell adhesion protein, which shares a homology with the insect cell adhesion molecule fasciclin I. It has been shown to be an important regulator of bone and tooth formation and maintenance, and of cardiac development and healing. Recent studies revealed that periostin plays an important role in tumor development and is upregulated in a wide variety of cancers such as colon, pancreatic, ovarian, breast, head and neck, thyroid, and gastric cancer as well as in neuroblastoma. Periostin binding to the integrins activates the Akt/PKB- and FAK-mediated signaling pathways which lead to increased cell survival, angiogenesis, invasion, metastasis, and importantly, epithelial-mesenchymal transition of carcinoma cells. In this review we summarize recent clinicopathological studies that have investigated periostin expression in lung, kidney, prostate, liver cancer, and malignant pleural mesothelioma and discuss the role of periostin isoforms in tumorigenesis and their potential as targets for stroma-targeted anticancer therapy

Neuroendokrine Tumoren der Niere

Die WHO-Klassifikation von 2004 der Nierentumoren unterscheidet bei den neuroendokrinen Tumoren u. a. das primäre Karzinoid und das primäre neuroendokrine Karzinom der Niere. Es handelt sich dabei um sehr seltene Tumoren. Bisher wurden etwa 100 primäre Karzinoide der Niere beschrieben. Die Histogenese der Nierenkarzinoide ist unklar, da in der Niere des Erwachsenen keine neuroendokrinen Zellen nachweisbar sind. Das histologische Bild der primären Nierenkarzinoide ähnelt denen der Karzinoide in anderen anatomischen Lokalisationen. Häufig werden Karzinoide der Niere fehldiagnostiziert und für papilläre Nierenzellkarzinome, mesonephrische Tumoren, Wilms-Tumoren oder undifferenzierte Karzinome gehalten. Obwohl es sich bei den primären Karzinoiden der Niere um einen Tumor von niedrigem Malignitätspotenzial handelt, wird häufig eine Metastasierung beobachtet. Dies betrifft v. a. Tumoren mit erhöhter Mitoserate (> 2 Mitosen/10 „high power field“ [HPF]). Es wird vorgeschlagen, den Begriff „primäres Karzinoid der Niere“ zu verlassen. Eine künftige WHO-Klassifikation der neuroendokrinen Tumoren sollte sich an Empfehlungen bei anderen Organen orientieren und zwischen neuroendokrinen Tumoren und neuroendokrinen Karzinomen der Niere unterscheiden. The 2004 World Health Organization (WHO) classification of renal cancer includes renal carcinoid and neuroendocrine cancer of the kidneys in the group of primary renal neuroendocrine tumors. The histological features of primary renal carcinoids are similar to those of neuroendocrine tumors found in other anatomical locations. Primary carcinoid tumors of the kidneys are frequently misdiagnosed as other kidney cancers, such as papillary renal cell carcinoma, mesonephric tumors, Wilms tumor (WT) and undifferentiated carcinoma. Immunohistochemical staining results are consistent with the diagnosis of a neuroendocrine tumor with immunoreactivity for synaptophysin, chromogranin, CD56, and neuron-specific enolase (NSE). Positive expression of CD99 can also be seen. There is mainly absence of WT1, cytokeratin 7, cytokeratin 20, thyroid transcription factor (TTF1) and LCA, ruling out most other differential diagnoses. Renal carcinoid tumors are regarded as low-grade neuroendocrine tumors; however, many studies have demonstrated metastatic disease in patients with renal carcinoid tumors. The prognostic value of histological parameters is uncertain. Some studies have correlated poor patient prognosis with increased mitotic activity, presence of necrosis and cytological atypia. Cases with higher mitotic rates of > 2 mitoses/10 high power fields (HPF) developed metastases more frequently; therefore, the WHO classification of neuroendocrine tumors used in other organs is recommended for primary renal carcinoid tumors

Klassifikation und molekulare Veränderungen des Nierenzellkarzinoms

Unter dem Begriff Nierenzellkarzinom werden unterschiedliche Tumortypen zusammengefasst. Ihre Kenntnis hat Einfluss auf die Auswahl neuer Behandlungsstrategien. Die International Society of Uropathology(ISUP) hat Vorschläge erarbeitet, auf deren Grundlage die derzeitige World-Health-Organization-(WHO)- Klassifikation der Nierentumoren (von 2004) angepasst werden wird. Dabei werden neue molekulare Erkenntnisse berücksichtigt, und die Klassifikation der Nierentumoren wird um neue Tumortypen erweitert

Papillary renal cell carcinoma: current and controversial issues

PURPOSE OF THE REVIEW Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC. RECENT FINDINGS It has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes. SUMMARY In the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup

Quantifying cancer progression with conjunctive Bayesian networks

Motivation: Cancer is an evolutionary process characterized by accumulating mutations. However, the precise timing and the order of genetic alterations that drive tumor progression remain enigmatic. Results: We present a specific probabilistic graphical model for the accumulation of mutations and their interdependencies. The Bayesian network models cancer progression by an explicit unobservable accumulation process in time that is separated from the observable but error-prone detection of mutations. Model parameters are estimated by an Expectation-Maximization algorithm and the underlying interaction graph is obtained by a simulated annealing procedure. Applying this method to cytogenetic data for different cancer types, we find multiple complex oncogenetic pathways deviating substantially from simplified models, such as linear pathways or trees. We further demonstrate how the inferred progression dynamics can be used to improve genetics-based survival predictions which could support diagnostics and prognosis. Availability: The software package ct-cbn is available under a GPL license on the web site cbg.ethz.ch/software/ct-cbn Contact: [email protected]

Human epidermal growth factor receptor 2 expression in early breast cancer patients: a Swiss cost-effectiveness analysis of different predictive assay strategies

Trastuzumab has conferred significant clinical benefits in HER-2-positive breast carcinomas. HER-2 status is determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridisation (FISH), but appropriate assessment of HER2 status remains subject to considerable debate. Data on the health economic impact of HER-2 test strategies are limited. A life-long Markov state transition model was used to assess costs and effectiveness of HER-2 assay strategies (based on IHC, FISH, both combined or FISH confirmation of IHC2+) for a hypothetical cohort of early breast cancer patients from the perspective of the Swiss health system. We compared clinically relevant strategies of predictive testing and subsequent trastuzumab treatment of HER-2-positive patients only. FISH testing was the most cost-effective strategy with an incremental cost-effectiveness ratio of €12,245 per additional quality-adjusted life-year (QALY) gained, compared to no trastuzumab treatment. The next best strategy was parallel IHC and FISH, with costs of €400,154/QALY gained compared to FISH alone. FISH as primary HER-2 testing modality remained the preferred option in deterministic and probabilistic sensitivity analysis. Predictive testing to identify adjuvant breast cancer patients who benefit from trastuzumab treatment is a clinical and economic necessity. Our model identifies FISH as the most cost-effective approac

Probing Isoform Switching Events in Various Cancer Types: Lessons From Pan-Cancer Studies

Alternative splicing is an essential regulatory mechanism for gene expression in mammalian cells contributing to protein, cellular, and species diversity. In cancer, alternative splicing is frequently disturbed, leading to changes in the expression of alternatively spliced protein isoforms. Advances in sequencing technologies and analysis methods led to new insights into the extent and functional impact of disturbed alternative splicing events. In this review, we give a brief overview of the molecular mechanisms driving alternative splicing, highlight the function of alternative splicing in healthy tissues and describe how alternative splicing is disrupted in cancer. We summarize current available computational tools for analyzing differential transcript usage, isoform switching events, and the pathogenic impact of cancer-specific splicing events. Finally, the strategies of three recent pan-cancer studies on isoform switching events are compared. Their methodological similarities and discrepancies are highlighted and lessons learned from the comparison are listed. We hope that our assessment will lead to new and more robust methods for cancer-specific transcript detection and help to produce more accurate functional impact predictions of isoform switching events