Prognostic Significance of Lacunarity in Preoperative Biopsy of Colorectal Cancer
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ORIGINAL ARTICLE
Prognostic Significance of Lacunarity in Preoperative Biopsy of Colorectal Cancer Gorana Aralica 1,2 & Martina Šarec Ivelj 1 & Arijana Pačić 2 & Josip Baković 2 & Marija Milković Periša 1 & Anteja Krištić 1 & Paško Konjevoda 3 Received: 4 February 2020 / Revised: 10 June 2020 / Accepted: 11 June 2020 # Arányi Lajos Foundation 2020
Abstract The quantity and quality of preoperative material in colorectal cancer is often limiting factor in determination of risk factors and therapy planning. The most important negative prognostic factors are intravascular and perineural invasion, as well as tumor budding. Usually, the only parameter available in preoperative biopsy is tumor budding. However, the growing body of evidence suggests that cancer differentiation based on the poorly differentiated clusters has better prognostic value. The limiting factor in applying of these new parameters is reproducible, simple, cheap and fast method of their determination. In this paper we investigated the prognostic value of lacunarity, determined in preoperative biopsy. Lacunarity is a measure of spatial heterogeneity (inhomogeneity) in an image. It quantifies how objects fill the space, and enables analysis of gaps distribution, homogeneity of gaps, and presence of structures. It was shown that lacunarity and the total number of buds could be combined in a model which clearly divides colorectal cancer patients in low, medium and high risk subgroups. The paper also points out that the quantitative numerical methods are superior to semiquantitative methods, and that individual methods should be combined using algorithms to obtain a more accurate prediction. Because the study described is designed as a pilot study, verification is needed on a larger sample of patients from independent researchers. Keywords Colorectal cancer . Preoperative biopsy . Intratumoral budding . Lacunarity . Prognosis . Recursive partitioning . Image analysis
Introduction Single cells detached from the tumor glands as an invasive parameter were first recognized by Japanese and American authors more than 40 years ago [1–3]. They have investigated detached tumor cells in the invasive tumor margin. The result of these studies was the definition of tumor budding as the finding of single tumor cell or small group up to five cells separated from the tumor invasive front [4]. These papers were followed by a large number of studies, which mainly went in two directions. One direction was to investigate the molecular properties of these cells, which led
* Gorana Aralica [email protected] 1
Medical School University of Zagreb, Zagreb, Croatia
2
University Hospital Dubrava, Zagreb, Croatia
3
Ruđer Bošković Institute, Zagreb, Croatia
to the concept of epithelial-mesenchymal transition (EMT) [5, 6]. These malignant epithelial cells adopt mesenchymal characteristics and thus enhanced invasiveness. Another direction of research is the attempts to suggest the optimal method of tumor budding quantification [3, 7–11]. Different groups proposed budding assessm
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