Clinical importance of molecular determinations in gynecologic patients with multiple tumors

Dinjens, Winand N.M.; Burg, M.E.L. van der; Chadha, S.; Sleddens, F B M M T Hein; Burger, Curt W.; Ewing, Marcela

doi:10.1002/cncr.11249

Cited by 6 publications

(8 citation statements)

References 38 publications

(71 reference statements)

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“…Genomic aberrations may increase our understanding of tumor progression giving us information about clonal origin. Indeed, by comparing the genetic aberration profiles of two different lesions, it is feasible to infer clonal origin, whereby a mutation pattern may be considered as a genetic clonal marker, and different aberration profiles may indicate independent primary tumors [ 38 , 39 ]. Although genomic aberrations are a feature of nearly all human cancers and their accumulation takes place over time during tumor genesis and progression, mutations or LOH found in advanced-stage cancers may be absent from the early-stage mass, even if the lesions share the same clonal origin.…”

Section: Currently Used Molecular Analyses To Infer Tumor Clonalitmentioning

confidence: 99%

Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies

Perrone,

Girolimetti,

Procaccini

et al. 2018

IJMS

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In the event of multiple synchronous gynecological lesions, a fundamental piece of information to determine patient management, prognosis, and therapeutic regimen choice is whether the simultaneous malignancies arise independently or as a result of metastatic dissemination. An example of synchronous primary tumors of the female genital tract most frequently described are ovarian and endometrial cancers. Surgical findings and histopathological examination aimed at resolving this conundrum may be aided by molecular analyses, although they are too often inconclusive. High mitochondrial DNA (mtDNA) variability and its propensity to accumulate mutations has been proposed by our group as a tool to define clonality. We showed mtDNA sequencing to be informative in synchronous primary ovarian and endometrial cancer, detecting tumor-specific mutations in both lesions, ruling out independence of the two neoplasms, and indicating clonality. Furthermore, we tested this method in another frequent simultaneously detected gynecological lesion type, borderline ovarian cancer and their peritoneal implants, which may be monoclonal extra-ovarian metastases or polyclonal independent masses. The purpose of this review is to provide an update on the potential use of mtDNA sequencing in distinguishing independent and metastatic lesions in gynecological cancers, and to compare the efficiency of molecular analyses currently in use with this novel method.

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Section: Currently Used Molecular Analyses To Infer Tumor Clonalitmentioning

confidence: 99%

Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies

Perrone,

Girolimetti,

Procaccini

et al. 2018

IJMS

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“…Several different approaches have been tried, including immunohistochemistry, flow cytometry (to compare chromosome ploidy), X-chromosome inactivation, and sequence analysis of genes frequently mutated during tumor progression (e.g., TP53). However, these have all been shown to have limited use in refining the relationship between dual site cancers (13)(14)(15)(16)(17)(18)(19).…”

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confidence: 99%

Predicting Clinical Outcome in Patients Diagnosed with Synchronous Ovarian and Endometrial Cancer

Ramus

Elmasry

Luo

et al. 2008

Clinical Cancer Research

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Purpose: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP).The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis. Experimental Design: In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers.We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses. Results: Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019). Conclusions: Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.

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“…8. Some earlier studies actually have provided evidence that the occurrence of some multiple tumors (MTs) is not due to migration of tumor cells because the tumor cells in different sites are not clonally related [ 84 , 85 ] based on the use of some "clonal" markers [ 86 , 87 ]. However, the use of identity or similarity in "clonal" markers as the only differentiation criterion for distinguishing clonally linked or independent tumor/cancer formation may be misleading.…”

Section: Hypothesis and Rationalesmentioning

confidence: 99%

“…We should emphasize that our proposal of a multigenesis mechanism for the occurrence of multi-site cancer does not dispute the occurrence of metastasis which may be even the prevalent cause for many of the multi-site cancers [ 98 - 100 ]. In some cases, the multi-site cancers in a patient may reflect the outcomes of both processes [ 85 ]. However, embracing a multigenesis view of multi-site cancer formation may provide additional insights into a comprehensive understanding of the cancer biology and thorough guidance on cancer therapy.…”

Section: Implications and Impactmentioning

confidence: 99%

Occurrence of cancer at multiple sites: Towards distinguishing multigenesis from metastasis

Zhang

et al. 2008

Biol Direct

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Background: Occurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs) has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms.

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Clinical importance of molecular determinations in gynecologic patients with multiple tumors

Abstract: Yanking the chain: A general method for the preparation of colloidal analogues of polymer chains was developed (see picture). The flexibility of these chains can be tuned by applying electric fields in combination with their subjection to simple linkage‐forming procedures.

Cited by 6 publications

References 38 publications

Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies

Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies

Predicting Clinical Outcome in Patients Diagnosed with Synchronous Ovarian and Endometrial Cancer

Occurrence of cancer at multiple sites: Towards distinguishing multigenesis from metastasis

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