Accuracy Analysis of a Next-Generation Tissue Microarray on Various Soft Tissue Samples of Wistar Rats  
[PERSON]  
1 Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany; [EMAIL_ADDRESS] (J.-E.W.);  
[EMAIL_ADDRESS] (S.M.); [PERSON]SS] (F.W.);  
[EMAIL_ADDRESS] (G.E.); [EMAIL_ADDRESS] (J.R.);  
[EMAIL_ADDRESS] (T.M.);  
[EMAIL_ADDRESS] (R.L.);  
and:[EMAIL_ADDRESS] (A.H.); [PERSON]S] (M.K.)  
[PERSON]  
2 Private Office for Maxillofacial Surgery, 97181 Westenburg, Germany 23 Department of Pathology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany; [EMAIL_ADDRESS] 24 Department of Oral and Maxillofacial Surgery, University of Mainz, 55131 Mainz, Germany;  
[EMAIL_ADDRESS] 4  
[PERSON], 33, 34  
inter-institutional research [14; 15]. Standard TMA methods require high expertise [14; 16], can be accompanied by loss of antigenicity [16; 17] and the loss of tissue cores [18; 19]. In addition, the informative value of a minuscule tissue punch when compared with whole slide analysis remains disputed [6; 15; 19; 20; 21; 22; 23]. Therefore, assessment of qualitative accuracy of ngTMA(r) has focused on determining how representative a punch core on a TMA is compared with a whole slide in immunohistochemical evaluation. Hence, there is advice on the number or diameter of cores for different tissue types such as breast cancer [20; 23], pulmonary cancer [15], colorectal cancer [24] and endometrial cancer [19]. By following these recommendations, a greater accuracy of the ngTMA(r) approach is assumed [11; 13; 14; 24].  
Due to the embryological derivation from branchial arches, different tissue types and anatomical structures of the midface, jaw and neck are in close vicinity to each other. Particular knowledge about the manageability of these different tissue types during the TMA construction is of importance when analysing samples of the head and neck region. Each TMA analysis suffers core loss [18] that depends on the tissue type, fixation method, core diameter and primary donor block thickness [18]. In the literature, core loss ranges between 5 and 35% [4; 7; 20; 21; 25; 26] for conventional TMAs and between 1 and 14% [5; 13; 19; 27; 28; 29; 30] for ngTMA(r)s. Though, in many analyses, core loss is not reported at all.  
Accuracy analysis of the ngTMA(r) method was done by [PERSON] et al. [13] by collecting data about the overall hit rates of the targeted structure. However, there is no study comparing different soft tissue types and accuracy in deeper sectional planes in a reproducible animal model.  
The primary aim of this study was to provide an in-depth accuracy analysis of the qualitative and quantitative accuracy of the ngTMA(r)-method in different soft tissue types and sectional planes, additionally providing metric measurements of the deviation from targeted structures. For this purpose, 40 ngTMA(r) were constructed using twelve different tissue types, ranging from small and fragile histo-anatomical structures to more homoge  
Figure 1: Workflow of automated TMA Production. One donor block is selected, and an H&E slide is made and digitalised. In this digital image, an annotation is marked. The Tissue-Microarray now takes a picture of the donor block, and a digital overlay with the annotated H&E slide is made by the operator. Now the annotated region is punched and transferred into the recipient TMA block. 3D sketches with kind permission of [PERSON]. [PERSON].  
nous tissues, such as parenchymal organs. Additionally, the total amount of core loss was recorded, as well as the amount of core loss in different tissue types.