Genotype-phenotype associations in colorectal adenocarcinomas and their matched metastases

Chatzopoulos, Kyriakos; Kotoula, Vassiliki; Koliou, Georgia-Angeliki; Giannoulatou, Eleni; Papadopoulou, Kyriaki; Karavasilis, Vasilios; Pazarli, Elissavet; Pervana, Stavroula; Kafiri, Georgia; Tsoulfas, Georgios; Chrisafi, Sofia; Sgouramali, Helen; Papakostas, Pavlos; Pectasides, Dimitrios; Hytiroglou, Prodromos; Pentheroudakis, George; Fountzilas, George

doi:10.1016/j.humpath.2020.10.009

Cited by 7 publications

(13 citation statements)

References 27 publications

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“…The data presented here refer to a study on geno/phenotyping in matched primary and metastatic colorectal carcinomas [1] that primarily describes differences in synchronous vs. metachronous metastases. FFPE tumor blocks were retrieved from the biologic material repository of the Hellenic Cooperative Oncology Group.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Hematoxylin & eosin (H&E) sections from an initial number of 235 FFPE blocks were examined for tumor presence and eligibility for the assessment of histological parameters [1] . Out of these, 170 FFPE blocks corresponding to 85 matched primary / metastatic tumor pairs (and to an equal number of patients) were considered eligible for both phenotypic evaluation and genotyping.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…For colorectal tumor genotyping [1] we used the IAD47763_31 Ampliseq panel (Applied Biosystems / Thermo Fisher Scientific). The panel was designed in 2013 to interrogate frequently mutated genes in colorectal cancer, as reported in the literature [ 8 , 9 , 10 ].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Samples eligible for analysis based on these criteria were: 158 out of 170 (92.9%) processed FFPE and 59 out of 65 (90.8%) processed germline DNA. However, 10 patients were subsequently removed from the geno/phenotyping study [1] due to incomplete clinical data or sample mismatches. Hence, the final number of patients was 75; for these, 141 FFPE tumor, 49 germline DNA genotypes and 2380 variants were analyzed.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…“Genotype – phenotype associations in colorectal adenocarcinomas and their matched metastases” is a study on geno/phenotyping in patient samples, matched primary and metastatic colorectal carcinomas [1] . FFPE tumor sample characteristics with respect to sample origin (site of primary and metastatic tumor), classification of metastasis with respect to elapsed time (synchronous or metachronous metastasis) based on histology report dates, as well as tumor cell content (TCC%), DNA content, and NGS data eligibility are included in the Supplementary File S1 dataset.…”

Section: Data Descriptionmentioning

confidence: 99%

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Genotyping data of routinely processed matched primary/metastatic tumor samples

et al. 2021

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Genotypic and phenotypic comparisons of tumors in multiple tissue samples from the same patient are important for understanding disease evolution and treatment possibilities. Panel NGS genotyping is currently widely used in this context, whereby NGS variant filtering and final evaluation constitute the basis for meaningful comparisons. Here, we present the genotype data used for genotype / phenotype comparisons between matched primary / metastatic colorectal tumors in the work by Chatzopoulos et al (doi: 10.1016/j.humpath.2020.10.009 ), as well as the process followed for obtaining these data. We describe key issues while processing routinely formalin-fixed paraffin-embedded (FFPE) tumors for genotyping, NGS application (Ion Torrent), a stringent variant filtering algorithm for genotype analyses in FFPE tissues and particularly in matched tumor samples, and provide the respective datasets. Apart from research, tumor NGS genotyping is currently applied for clinical diagnostic purposes in Oncology. The datasets and method description provided herein (a) are important for comprehending the peculiarities of FFPE tumor genotyping, which is still mostly based on principles of germline DNA genotyping; (b) can be used in pooled analyses, e.g., of primary / metastatic tumors for the investigation of tumor evolution.

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Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Data Descriptionmentioning

confidence: 99%

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Genotyping data of routinely processed matched primary/metastatic tumor samples

et al. 2021

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The different clonal origins of metachronous and synchronous metastases

Gofrit

Roditi

et al. 2023

J Cancer Res Clin Oncol

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Background Metastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes. Materials and methods We retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010–2020. Patient’s population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of 1 suggests pure linear dissemination and − 1 pure parallel. Results Patients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001). Conclusion Patients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions.

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Immunological and prognostic significance of tumour necrosis in colorectal cancer

et al. 2023

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Background Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC. Methods Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined. Results Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68–6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour. Conclusions Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.

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Genotype-phenotype associations in colorectal adenocarcinomas and their matched metastases

Cited by 7 publications

References 27 publications

Genotyping data of routinely processed matched primary/metastatic tumor samples

Genotyping data of routinely processed matched primary/metastatic tumor samples

The different clonal origins of metachronous and synchronous metastases

Immunological and prognostic significance of tumour necrosis in colorectal cancer

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