Vision Transformers for Small Histological Datasets Learned through Knowledge Distillation

Computational Pathology (CPATH) systems have the potential to automate diagnostic tasks. However, the artifacts on the digitized histological glass slides, known as Whole Slide Images (WSIs), may hamper the overall performance of CPATH systems. Deep Learning (DL) models such as Vision Transformers (ViTs) may detect and exclude artifacts before running the diagnostic algorithm. A simple way to develop robust and generalized ViTs is to train them on massive datasets. Unfortunately, acquiring large medical datasets is expensive and inconvenient, prompting the need for a generalized artifact detection method for WSIs. In this paper, we present a student-teacher recipe to improve the classification performance of ViT for the air bubbles detection task. ViT, trained under the student-teacher framework, boosts its performance by distilling existing knowledge from the high-capacity teacher model. Our best-performing ViT yields 0.961 and 0.911 F1-score and MCC, respectively, observing a 7% gain in MCC against stand-alone training. The proposed method presents a new perspective of leveraging knowledge distillation over transfer learning to encourage the use of customized transformers for efficient preprocessing pipelines in the CPATH systems.Comment: Accepted at PAKDD 202

A SNaPshot assay for the rapid and simple detection of four common hotspot codon mutations in the PIK3CA gene

<p>Abstract</p> <p>Background</p> <p>Activating mutations in the <it>PIK3CA </it>gene have been identified in a variety of human malignancies and are commonly detected in hotspot codons located in the helical and kinase domains in exons 9 and 20. Existing methodologies for the detection of <it>PIK3CA </it>mutations are time-consuming and/or expensive. In the present study we describe the first application of a <it>PIK3CA </it>SNaPshot assay to the screening of frequent mutations in these exons.</p> <p>Findings</p> <p>A SNaPshot assay for the simultaneous detection of four frequent PIK3CA hotspot mutations (E542K, E545G, E545K and H1047R) has been developed and evaluated. The assay combines multiplex PCR amplification with a multiplex primer extension assay to allow targeted detection of all four mutations in one reaction. The method was tested using samples that had previously been analysed for mutations by high-resolution melting analysis and sequencing. All mutations detected were concordant and no false positive results were obtained. Sensitivity tests showed that the SNaPshot assay could detect mutant DNA when it represents 5–10% of the total DNA present. The application of the method to the analysis of DNAs extracted from formalin-fixed paraffin-embedded samples was also demonstrated.</p> <p>Conclusion</p> <p>The SNaPshot assay described here offers a fast, sensitive, inexpensive and specific approach to the analysis of frequent <it>PIK3CA </it>mutations in both fresh and archival patient samples.</p

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: A case report

Background. The molecular characteristics and the clinical disease course of bladder cancer (BC) in young patients remain largely unresolved. All patients are monitored according to an intensive surveillance protocol and we aim to gain more insight into the molecular pathways of bladder tumors in young patients that could ultimately contribute to patient stratification, improve patient quality of life and reduce associated costs. We also determined whether a biomarker-based surveillance could be feasible. Case Presentation. We report a unique case of a 26-year-old Caucasian male with recurrent non-muscle invasive bladder tumors occurring at a high frequency and analyzed multiple tumors (maximal pTaG2) and urine samples of this patient. Analysis included FGFR3 mutation detection, FGFR3 and TP53 immunohistochemistry, mircosatellite analysis of markers on chromosomes 8, 9, 10, 11 and 17 and a genome wide single nucleotide polymorphism-array (SNP). All analyzed tumors contained a mutation in FGFR3 and were associated with FGFR3 overexpression. None of the tumors showed overexpression of TP53. We found a deletion on chromosome 9 in the primary tumor and this was confirmed by the SNP-array that showed regions of loss on chromosome 9. Detection of all recurrences was possible by urinary FGFR3 mutation analysis. Conclusions. Our findings would suggest that the BC disease course is determined by not only a patient's age, but also by the molecular characteristics of a tumor. This young patient contained typical genetic changes found in tumors of older patients and implies a clinical disease course comparable to older patients. We demonstrate that FGFR3 mutation analysis on voided urine is a simple non-invasive method and could serve as a feasible follow-up approach for this young patient presenting with an FGFR3 mutant tumor

Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Methods: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. Results: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4–15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. Conclusion: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient’s disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.The study was supported by The John and Birthe Meyer Foundation, the Danish Cancer Society, the Ministry of Technology and Science, and the Lundbeck Foundation. Furthermore, the research leading to these results has received funding from the European Community’s Seventh Framework program FP7/2007-2011 under grant agreement no. 201663