Digital analysis of distant and cancer-associated mammary adipocytes

Abstract

Adipocytes and cancer-associated adipocytes (CAAs) are poorly investigated cells in the tumor microenvironment. Different image analysis software exist for identifying and measuring these cells using scanned hematoxylin and eosin (H&E)-stained slides. It is however unclear which one is the most appropriate for breast cancer (BC) samples. Here, we compared three software (AdipoCount, Adiposoft, and HALO®). HALO® outperformed the other methods with regard to adipocyte identification, (> 96% sensitivity and specificity). All software performed equally good with regard to area and diameter measurement (concordance correlation coefficients > 0.97 and > 0.96, respectively). We then analyzed a series of 10 BCE samples (n = 51 H&E slides) with HALO®. Distant adipocytes were defined >2 mm away from cancer cells or fibrotic region, whereas CAAs as the first three lines of adipocytes close to the invasive front. Intra-mammary heterogeneity was limited, implying that measuring a single region of ∼500 adipocytes provides a reliable estimation of the distribution of their size features. CAAs had smaller areas (median fold-change: 2.62) and diameters (median fold-change: 1.64) as compared to distant adipocytes in the same breast (both p = 0.002). The size of CAAs and distant adipocytes was associated with the body mass index (BMI) of the patient (area: rho = 0.89, p = 0.001; rho = 0.71, p = 0.027, diameter: rho = 0.87 p = 0.002; rho = 0.65 p = 0.049, respectively). To conclude, we demonstrate that quantifying adipocytes in BC sections is feasible by digital pathology using H&E sections, setting the basis for a standardized analysis of mammary adiposity in larger series of patients.

Abstract P4-02-02: The association between adiposity and anti-proliferative response to neoadjuvant endocrine therapy with letrozole in post-menopausal patients with estrogen receptor positive breast cancer

“…Considering that BMI is inaccurate in describing the adiposity of specific fat depots, we also assessed mammary adipocyte size as alternative measure of mammary adiposity. In line with our previous work 22 , we showed a correlation between BMI and adipocyte size, although it is moderate. As for BMI, we found that adipocyte size (area and diameter) is a positive predictor of anti-proliferative response, showing that patients with larger distant adipocytes were more likely to have an anti-proliferative response.…”

Impact of obesity and white adipose tissue inflammation on the omental microenvironment in endometrial cancer

“…In the obesogenic state, adipose tissue hypertrophy can lead to adipocyte stress and death, ultimately triggering inflammation. Adipose tissue inflammation is histologically recognized when macrophages engulf dead or dying adipocytes, forming a crown‐like structure (CLS) 11 . The presence of CLS is indicative of inflammation in white adipose tissue (WAT) 2,11 .…”

“…Adipose tissue inflammation is histologically recognized when macrophages engulf dead or dying adipocytes, forming a crown‐like structure (CLS) 11 . The presence of CLS is indicative of inflammation in white adipose tissue (WAT) 2,11 . In breast and squamous cell carcinomas of the tongue, WAT inflammation represented by CLS not only correlates with multiple cardiometabolic disorders such as hyperlipidemia, hypertension, and diabetes, but also has a negative impact on progression‐free survival 6,12 .…”

“…11 The presence of CLS is indicative of inflammation in white adipose tissue (WAT). 2,11 In breast and squamous cell carcinomas of the tongue, WAT inflammation represented by CLS not only correlates with multiple cardiometabolic disorders such as hyperlipidemia, hypertension, and diabetes, but also has a negative impact on progression-free survival. 6,12 In prostate cancer, the presence of CLS has been associated with higher grade disease.…”

Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas

“…What should be the role of the surrounding and breast cancer-associated adipocytes? A few studies suggest that cancer-associated adipocytes can also cause resistance to radiotherapy and to chemotherapeutic drugs ( 209 , 210 ). Another study described that interaction between cancer-associated adipocytes and cancer cells seems to be more pronounced in obese patients ( 211 ).…”