Form follows function: Morphological and immunohistological insights into epithelial-mesenchymal transition characteristics of tumor buds.

In cancer biology, the architectural concept "form follows function" is reflected by cell morphology, migration, and epithelial-mesenchymal transition protein pattern. In vivo, features of epithelial-mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial-mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial-mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial-mesenchymal transition marker expression were assessed for each tumor cell. Epithelial-mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial-mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial-mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial-mesenchymal transition zinc finger E-box-binding homeobox 1-E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.

[German Translation and Validation of the Patient-Oriented Questionnaire "Thumb Disability Examination" (TDX) for Specific Diagnosis and Follow-Up of Thumb Carpometacarpal Joint Osteoarthritis]. / Deutsche Übersetzung und Validierung des patienten-orientierten Fragebogens "Thumb Disability Examination" (TDX) zur spezifischen Diagnostik und Verlaufskontrolle bei Rhizarthrose.

BACKGROUND: Patient-reported outcome measures (PROMs) are becoming increasingly important in today's patient care. Unfortunately, the most common PROMs in hand surgery are very time-consuming and usually do not cover the actual, diagnosis-specific complaints of the patients. For diagnosis and follow-up of thumb carpometacarpal joint osteoarthritis, Noback et al. developed and validated the Thumb Disability Examination (TDX) questionnaire. This 20-item questionnaire specifically assesses daily living limitations and pain as well as patient-reported satisfaction of thumb function. The aim of this study is to validate the German translation of the TDX, the Thumb Disability Examination - German (TDX-G), and to compare it with the German-language versions of the MHQ and qDASH, which are currently used as gold standard. MATERIAL UND METHODS: Translation and back-translation were performed in accordance with accepted guidelines. For statistical validation of the TDX-G, 30 consecutive patients with thumb carpometacarpal joint osteoarthritis were interviewed under standardised conditions. Internal consistency was calculated using Cronbach's alpha. Test-retest reliability was determined in 10 patients who completed the TDX-G twice at an interval of 2 weeks. The validity of the TDX-G was determined by calculating the correlation coefficients of the TDX-G with the MHQ and qDASH, subjective pain sensation (NRS), and hand strength levels (coarse and pinch strength). In addition, the time to collect each questionnaire was compared. RESULTS: The TDX-G has high internal consistency (Cronbach's alpha 0.932) and test-retest reliability (intraclass correlation coefficient 0.963 [0.850-0.991]). There is a significant correlation between TDX-G and MHQ (- 0.782; p<0.001) and qDASH (0.833; p<0.001). All questionnaires correlate significantly with pain on exertion and pinch force, with the TDX-G having the highest correlation in each case. Significantly less time is needed to record the TDX-G (110±28 s) than to record the MHQ (413±98 s). CONCLUSION: The TDX-G is a reliable tool for diagnosing and monitoring the progression of thumb carpometacarpal joint osteoarthritis. It can be used in both patient care and clinical research and accurately mirrors the symptoms.

Morphology of Immunomodulation in Breast Cancer Tumor Draining Lymph Nodes Depends on Stage and Intrinsic Subtype.

Cancer research of immune-modulating mechanisms mainly addresses the role of tumor-infiltrating immune cells. Mechanisms modulating the adaptive immune system at the primary activation site - the draining lymph node (LN) - are less investigated. Here we present tumor-caused histomorphological changes in tumor draining LNs of breast cancer patients, dependent on the localization (sentinel LN vs. non-sentinel LN), the tumor size, the intrinsic subtype and nodal metastatic status. The quantitative morphological study was conducted in breast cancer patients with at least one sentinel LN and no neoadjuvant therapy. All LNs were annotated considering to their topographical location, stained for IgD/H&E, digitized and quantitatively analyzed. In 206 patients, 394 sentinels and 940 non-sentinel LNs were categorized, comprising 40758 follicles and 7074 germinal centers. Subtype specific immunomorphological patterns were detectable: Follicular density was higher in LNs of Her2 enriched hormone receptor positive and triple-negative breast cancers whereas hormone receptor positive breast cancers showed more macrophage infiltrations in the LN cortex. Follicles are rounder in metastatic LNs and non-sentinel LNs. The identified immunomorphological changes reflect different underlying immunomodulations taking place in the tumor-draining LNs and should therefore be considered as possible prognostic and predictive markers for LN metastasis and therapy associated immunomodulation.