White adipose tissue inflammation and cancer‐specific survival in patients with squamous cell carcinoma of the oral tongue

Iyengar, Neil M.; Ghossein, Ronald; Morris, Luc G.T.; Zhou, Xi Kathy; Kochhar, Amit; Morris, Patrick G.; Pfister, David G.; Patel, Snehal G.; Boyle, Jay O.; Hudis, Clifford A.; Dannenberg, Andrew J.

doi:10.1002/cncr.30251

Cited by 46 publications

(43 citation statements)

References 54 publications

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“…Other studies have been implemented in cancers of the gastrointestinal tract (colorectal cancer (n=4) (8,64,71,73), esophageal cancer (n=2) (65,79), combined (colorectal and esophageal) (n=1) (80)), reproductive cancer (endometrial (n=1) (72), prostate (n=4) (69,74,81,82)), or ENT tract (tongue (n=1) (83)).…”

Section: Resultsmentioning

confidence: 99%

“…To assess the association between WAT inflammation of the tongue environmental adipose tissue and squamous cell carcinoma (SCC) of the tongue, Iyengar et al analyzed n=125 tissue samples from oral cancer patients (83). The presence of dead or dying adipocytes surrounded by macrophages forming crown-like structures was defined as WAT inflammation (83).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…The presence of dead or dying adipocytes surrounded by macrophages forming crown-like structures was defined as WAT inflammation (83). Thirty-nine percent of the patients presented WAT inflammation, and this was statistically significant associated with BMI, increased tumor thickness, and vascular invasion (p<0.05) (83). The cancer-specific survival rate was with 59% (95% CI, 46–76%) lower for patients presenting WAT inflammation compared to patients without (82%; 95% CI, 72–92%) (83).…”

Section: Resultsmentioning

confidence: 99%

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Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Himbert

Delphan

Scherer

et al. 2017

Cancer Prevention Research

157

131

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Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiological, clinical, and preclinical data suggest that within the growth-promoting, pro-inflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct “crosstalk” between adipose tissue and carcinomas in humans. We identified 4,641 articles with n=20 human clinical studies which are summarized as: (a) breast (n=7), (b) colorectal (n=4), (c) esophageal (n=2), (d) esophageal/colorectal (n=1), (e) endometrial (n=1), (f) prostate (n=4), and (g) ear-nose-throat (ENT) cancer (n=1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL-6, TNF-alpha and other mechanisms. Moreover, visceral white adipose tissue (VAT) plays a more central role as it is more bio-energetically active and is associated with a more pro-cancer secretome than subcutaneous adipose tissue (SAT). Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Himbert

Delphan

Scherer

et al. 2017

Cancer Prevention Research

157

131

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“…It is also likely that breast WAT inflammation and its associated systemic alterations promote tumors via hormone-dependent and independent mechanisms. For example WAT inflammation in the tongue confers shortened disease specific survival for patients with early stage squamous cell carcinoma of the oral tongue, a disease that is not thought to be hormonally regulated (47). Insulin can stimulate the synthesis of insulin-like growth factor 1 (IGF-1) and both can activate the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways which are linked to breast tumor progression (48–50).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index

Iyengar

Brown

Zhou

et al. 2017

Cancer Prevention Research

Self Cite

124

127

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Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen-biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (< 25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are comprised of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine if breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 (range 18.4 to 24.9) in women with breast WAT inflammation versus 21.8 (range 17.3 to 24.6) in those without inflammation (P=.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P<.05). Breast WAT inflammation correlated with larger adipocytes (P=.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P≤.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer.

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Predicting lymph node recurrence in cT1‐2N0 tongue squamous cell carcinoma: collaboration between artificial intelligence and pathologists

Adachi,

Taki,

Kojima

et al. 2024

The Journal of Pathology CR

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Researchers have attempted to identify the factors involved in lymph node recurrence in cT1‐2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1‐2, N0 (cT1‐2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1‐2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI‐extracted information from whole slide images (WSIs), human‐assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non‐recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non‐recurrence cases. The model integrating AI‐extracted histopathological and human‐assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1‐2N0 tongue SCC.

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White adipose tissue inflammation and cancer‐specific survival in patients with squamous cell carcinoma of the oral tongue

Cited by 46 publications

References 54 publications

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index

Predicting lymph node recurrence in cT1‐2N0 tongue squamous cell carcinoma: collaboration between artificial intelligence and pathologists

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