Clear Cell Renal Cell Carcinomas with Aggressive Behavior Display Low Intratumor Heterogeneity at the Histological Level

Manini, Claudia; López-Fernández, Estíbaliz; Lawrie, Charles H.; Laruelle, Annick; Angulo, Javier C.; López, José I.

doi:10.1007/s11934-022-01095-9

Cited by 7 publications

(11 citation statements)

References 21 publications

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“…This study demonstrates that branched-type tumors have mutations constrained to VHL, PBRM1, SETD2, PI3K genes, display high levels of genomic ITH, present low levels of chromosomal complexity, pursue an attenuated clinical course, and develop late, solitary metastases. This association between the level of ITH and tumor aggressiveness has been corroborated in a recent histological study of 28 exhaustively sampled CCRCC [13] .…”

supporting

confidence: 58%

Pathology and the evolutionary dynamics of clear cell renal cell carcinoma

Manini

López

2023

Translational Oncology

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supporting

confidence: 58%

Pathology and the evolutionary dynamics of clear cell renal cell carcinoma

Manini

López

2023

Translational Oncology

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“…2 and 3 , recall that following the empirical oncology study in Manini et al. ( 2022 ), ITH is considered as low when the tumor has two different cell populations (grades) measured by histological parameters. Such tumors are represented in our model by 2-type population games.…”

Section: Discussionmentioning

confidence: 99%

“…The two types of tumor analysis agree that low ITH (corresponding to the punctuated evolutionary pattern) is more aggressive than high ITH ( corresponding to the branching pattern) (Manini et al. 2022 ; Turajlic et al. 2018b ).…”

Section: A Case Studymentioning

confidence: 92%

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Effects of Heterogeneity on Cancer: A Game Theory Perspective

et al. 2023

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In this study, we explore interactions between cancer cells by using the hawk–dove game. We analyze the heterogeneity of tumors by considering games with populations composed of 2 or 3 types of cell. We determine what strategies are evolutionarily stable in the 2-type and 3-type population games and what the corresponding expected payoffs are. Our results show that the payoff of the best-off cell in the 2-type population game is higher than that of the best-off cell in the 3-type population game. When these mathematical findings are transferred to the field of oncology they suggest that a tumor with low intratumor heterogeneity pursues a more aggressive course than one with high intratumor heterogeneity. Some histological and genomic data on clear cell renal cell carcinomas is consistent with these results. We underline the importance of identifying intratumor heterogeneity in routine practice and suggest that therapeutic strategies that preserve heterogeneity may be promising as they may slow down cancer growth.

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“…For example, spontaneous tumor necrosis is a common finding in large tumors which can be detected by the naked eye and is always related to high grade. Low ITH at histological and genomic levels are characteristic findings in many aggressive CCRCC [ 6 , 25 ]. In consequence, it can be inferred even in the grossing room that tumors showing areas of necrosis will have high-grade histological features and low levels of ITH.…”

Section: Personalized Multisite Tumor Sampling (Pmsts)mentioning

confidence: 99%

Towards Personalized Sampling in Clear Cell Renal Cell Carcinomas

Manini

López-Fernández

López

2022

Cancers

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Intratumor heterogeneity (ITH) is a constant evolutionary event in all malignant tumors, and clear cell renal cell carcinoma (CCRCC) is a paradigmatic example. ITH is responsible for most therapeutic failures in the era of precision oncology, so its precise detection remains a must in modern medicine. Unfortunately, classic sampling protocols do not resolve the problem as expected and several strategies have been being implemented in recent years to improve such detection. Basically, multisite tumor sampling (MSTS) and the homogenization of the residual tumor tissue are on display. A next step of the MSTS strategy considering the recently discovered patterns of ITH regionalization is presented here, the so-called personalized MSTS (pMSTS). This modification consists of paying more attention to sample the tumor periphery since it is this area with maximum levels of ITH.

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Clear Cell Renal Cell Carcinomas with Aggressive Behavior Display Low Intratumor Heterogeneity at the Histological Level

Cited by 7 publications

References 21 publications

Pathology and the evolutionary dynamics of clear cell renal cell carcinoma

Pathology and the evolutionary dynamics of clear cell renal cell carcinoma

Effects of Heterogeneity on Cancer: A Game Theory Perspective

Towards Personalized Sampling in Clear Cell Renal Cell Carcinomas

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