Tumour heterogeneity and resistance to cancer therapies

Dagogo‐Jack, Ibiayi; Shaw, Alice T.

doi:10.1038/nrclinonc.2017.166

Cited by 2,662 publications

(2,052 citation statements)

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“…Intertumor heterogeneity comprises differences in tumors of the same histologic type between patients, and, more rarely, differences in synchronic colorectal tumors occurring within a single patient. Intratumor heterogeneity can be subdivided into spatial and temporal heterogeneity [4]. Spatial heterogeneity refers to differences that can be observed within a single tumor, i.e., either different genetic subpopulations within the primary tumor site or differences between the primary tumor and its metastatic lesions [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Sagaert¹,

Vanstapel²,

Verbeek³

2018

Pathobiology

138

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Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy. Recently, 4 distinct molecular subtypes of colorectal cancer have been described that have both prognostic and therapeutic relevance. In addition, characterization of the inflammatory infiltrate revealed major differences in the amount and location of inflammatory cells in distinct colorectal tumor types. Together, all of these parameters help to stratify patients into different therapeutic and prognostic subgroups. However, this stratification is not unambiguous since tumors often display intratumoral heterogeneity, whereby several subpopulations within one tumor show differences in morphology, inflammatory infiltrate, mutational status, or gene expression profile. This article gives an overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels.

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Section: Introductionmentioning

confidence: 99%

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Sagaert¹,

Vanstapel²,

Verbeek³

2018

Pathobiology

138

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“…[26] However, in our study, all our cases that were p16 positive showed diffuse p16 expression, thus did not show tumor heterogeneity. This is particularly important.…”

Section: Ent Updatesmentioning

confidence: 53%

Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance

Çelebi¹,

Şener²,

Aydın³

et al. 2018

ENT Updates

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Özet: Normal ve tümöral orofaringeal dokuda in situ hibridizasyon ve p16 ekspresyonu ile human papilloma virüsü varl›¤›n›n de¤erlendirilmesi ve klinikopatolojik önemiAmaç: Human papilloma virüs (HPV) pozitif orofaringeal hücreli kanser olgular›nda son y›llarda görülen art›fl, bu virüsün tespitinin klinik önemini art›rmaktad›r. Bu çal›flmada amac›m›z orofaringeal kanser hastalar›m›z›n HPV pozitiflik oranlar›n› bulmak, farkl› HPV tespit yöntemleri olan p16 immünohistokimya (IHC) ve in situ hibridizasyonunun (ISH) etkinli¤ini karfl›laflt›rarak boyanma paternlerini göstermektir. Yöntem:Retrospektif dosya taramas› ile bulunan 23 hasta ve 10 kontrol çal›flmaya dahil edilerek hastalar›n patoloji arflivinden bulunan parafin bloklar›nda p16 IHC ve HPV ISH çal›fl›ld›. Bulgular:Yirmi üç olgunun 7'si p16 pozitif idi. Bunlar›n alt›s› yüksek p16 ekspresyonu gösterirken biri düflük p16 ekspresyonu göstermek-teydi. 23 olgunun alt›s› ISH pozitif idi. Yüksek p16 ekspresyonu gös-teren tüm olgular HPV ISH pozitif iken düflük ekspresyon gösteren bir olgu HPV ISH negatif idi. Tüm p16 pozitif olgular diffüz p16 ekspresyonu göstermekteydi, dolay›s›yla tümör heterojenitesi gösterme-mekteydi.Sonuç: Yüksek p16 ekspresyonu (>%70) HPV pozitifli¤inin güvenilir bir göstergesidir ve p16 IHC ile kombine etmek spesifitesini art›rmak-tad›r. Olgular tümör heterojenitesi göstermemekte, dolay›s›yla al›nan az miktarda biyopsi parças›nda bile p16 ekspresyonunun gözlenmesi bize tüm tümöral dokuda p16 ekspresyonu oldu¤unu göstermektedir.Anahtar sözcükler: Human papilloma virüs, orofaringeal kanser, p16 immunohistokimya, in situ hibridizasyon. AbstractObjective: The rise in the number of cancer cases with human papilloma virus (HPV)-positive squamous carcinoma of the oropharynx makes the detection of HPV clinically important. We aimed to investigate the HPV positivity in our patients who have oropharyngeal cancer and compare the two different HPV detection methods, which are HPV in situ hybridization (ISH) and p16 immunohistochemistry (IHC), and show the staining patterns.Methods: Twenty-three specimens of oropharyngeal cancer patients and ten tonsillectomy specimens that revealed no cancerous tissue (control group) were collected from retrospective file analysis. All specimens were evaluated by both p16 IHC and HPV ISH on paraffin blocks.Results: Seven of 23 cases showed p16 expression. Of all these 7 cases that showed p16 expression, six showed high p16 expression and one showed low p16 expression. All six cases that showed high p16 expression were HPV ISH (+). One case that showed low expression of p16 was HPV ISH (-). All cases that were p16 (+) showed diffuse p16 expression and none of the cases showed focal p16 expression. Conclusion:High p16 expression (>70%) is a reliable marker of HPV positivity. Combining p16 IHC with HPV ISH will further improve its specificity. All p16 positive cases showed diffuse p16 expression, thus did not show tumor heterogeneity, suggesting that even a biopsy specimen showing diffuse p16 expression shows p16 positivity ...

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“…Die intertumorale Heterogenität beinhaltet Unterschiede bei Tumoren des gleichen histologischen Typs zwischen den Patienten und - seltener - Unterschiede in gleichzeitig auftretenden CRC bei einem einzelnen Patienten. Die intratumorale Heterogenität lässt sich in räumliche und zeitliche Heterogenität unterteilen [4]. Die räumliche Heterogenität bezieht sich auf die Unterschiede, die innerhalb eines einzelnen Tumors zu beobachten sind, d.h. entweder unterschiedliche genetische Subpopulationen innerhalb des Primärtumors oder Unterschiede zwischen dem Primärtumor und seinen metastatischen Läsionen [5,6].…”

Section: Introductionunclassified

Tumorheterogenität des kolorektalen Karzinoms: Was wir bisher wissen

Vanstapel¹,

Verbeek²

2019

Kompass Onkol

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Das Kolorektalkarzinom ist keine einzelne Erkrankung, sondern umfasst vielmehr eine Gruppe von neoplastischen Erkrankungen. Aufgrund der Heterogenität der Erkrankung sowie des Therapieansprechens und der Prognose ist eine umfangreiche Stratifizierung der Krankheit erforderlich. Daher werden im Pathologiebericht TNM-Stadium, Mikrosatellitenstatus, Tumorgrad, Lymphgefäßeinbruch und andere Parameter bewertet, um das Ausmaß und die Prognose der Erkrankung aufzuzeigen. Ferner wird bei einer Metastasierung der KRAS-, BRAF- und NRAS-Mutationsstatus untersucht, um das Ansprechen auf eine Anti-EGFR-Therapie (EGFR = epidermaler Wachstumsfaktorrezeptor) vorherzusagen. Kürzlich wurden 4 unterschiedliche molekulare Subtypen des Kolorektalkarzinoms beschrieben, die sowohl von prognostischer als auch von therapeutischer Relevanz sind. Darüber hinaus zeigten sich in der Untersuchung des entzündlichen Infiltrats wesentliche Unterschiede hinsichtlich der Anzahl und Lokalisation der Entzündungszellen bei den verschiedenen Kolorektalkarzinomtypen. Die Gesamtheit dieser Parameter ermöglicht eine Stratifizierung der Patienten in verschiedene therapeutische und prognostische Subgruppen. Eine solche Stratifizierung ist jedoch nicht eindeutig, da Tumoren häufig intratumorale Heterogenität aufweisen, bei der verschiedene Subpopulationen innerhalb eines Tumors Unterschiede hinsichtlich Morphologie, entzündlichem Infiltrat, Mutationsstatus oder Genexpressionsprofil zeigen. Der vorliegende Artikel gibt einen Überblick über alle derzeit bekannten Daten zur Tumorheterogenität sowohl auf inter- als auch auf intratumoraler Ebene.

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Tumour heterogeneity and resistance to cancer therapies

Cited by 2,662 publications

References 127 publications

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance

Tumorheterogenität des kolorektalen Karzinoms: Was wir bisher wissen

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