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Multi-site tumor sampling (MSTS) improves the performance of histological detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC).

ABSTRACT: Current standard-of-care tumor sampling protocols for CCRCC (and other cancers) are not efficient at detecting intratumoural heterogeneity (ITH). We have demonstrated in silico that an alternative protocol, multi-site tumor sampling (MSTS) based upon the divide and conquer (DAC) algorithm, can significantly increase the efficiency of ITH detection without extra costs. Now we test this protocol on routine hematoxylin-eosin (HE) sections in a series of 38 CCRCC cases. MSTS was found to outperform traditional sampling when detecting either high grade (p=0.0136) or granular/eosinophilic cells (p=0.0114). We therefore propose that MSTS should be used in routine clinical practice.

SUBMITTER: Guarch R

PROVIDER: S-EPMC5007747 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Multi-site tumor sampling (MSTS) improves the performance of histological detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC).

Guarch Rosa R Cortés Jesús M JM Lawrie Charles H CH López José I JI

F1000Research 20160817

Current standard-of-care tumor sampling protocols for CCRCC (and other cancers) are not efficient at detecting intratumoural heterogeneity (ITH). We have demonstrated <i>in silico</i> that an alternative protocol, multi-site tumor sampling (MSTS) based upon the divide and conquer (DAC) algorithm, can significantly increase the efficiency of ITH detection without extra costs. Now we test this protocol on routine hematoxylin-eosin (HE) sections in a series of 38 CCRCC cases. MSTS was found to outp ...[more]

PMID: 27635226

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Project description:To discuss the dual energy spectral computer tomography (CT) imaging features of the pathological grading of clear cell renal cell carcinoma (ccRCC) and the correlation between spectral CT imaging features and pathology.We performed analyses of 62 patients with confirmed diagnosis of ccRCC. All patients underwent non-enhanced CT and dual-phase (cortex phase, CP and parenchyma phase, PP) contrast-enhanced CT with dual energy spectral mode. The subjects were pathologically divided into two groups: low-grade group (Fuhrman 1/2) and high-grade group (Fuhrman 3/4). The CT value of each lesion was measured on the monochromatic image at 70 keV. The normalized iodine concentrations (NIC) and the slope of the spectrum curve were calculated. The qualitative morphological parameters, including tumor shape, calcification, pseudocapsule, necrosis, and enhancement mode, were compared between the two groups. The quantitative data were compared using Student's t-test, and the enumeration data were analyzed using the chi-square test between low-grade and high-grade ccRCC.Receiver operating characteristic curve was used to determine the sensitivity and specificity of the quantitative parameters in two groups.The CT value, NIC, and mean slope of the low-grade group were increased compared with the high-grade group during CP (P = 0.001, P = 0.043, and P<0.001, respectively). The CT did not differ significantly during PP (P = 0.134); however, the NIC and mean slope varied considerably in the low grade compared with the high-grade group (P = 0.048, P = 0.017, respectively). The CT threshold value, NIC, and slope had high sensitivity and specificity in differentiating low-grade ccRCC from high-grade ccRCC. The tumor shape, pseudocapsule, and necrosis differed significantly between the two groups (P<0.05).Dual energy spectral CT with the quantitative analysis of iodine concentration and qualitative analysis of morphological characteristics increases the accuracy of diagnosing the pathological grade of ccRCC.

Project description:Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

Dataset Information

Multi-site tumor sampling (MSTS) improves the performance of histological detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC).

Publications

Multi-site tumor sampling (MSTS) improves the performance of histological detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC).

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