Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST) in Colorectal Cancer is Associated with an Elderly, Frail Phenotype and Improved Recurrence-Free Survival

Watson, Martin M.; Kanani, Arezo; Lea, Dordi; Khajavi, Ramesh B.; Søreide, Jon Arne; Kørner, Hartwig; Hagland, Hanne R.; Søreide, Kjetil

doi:10.1245/s10434-019-08048-6

Cited by 15 publications

(15 citation statements)

References 37 publications

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“…All patients were diagnosed, managed and followed-up at Stavanger University Hospital (SUH), a public-funded university hospital within the universal health care system of Norway. The protocol [ 18 ] and study cohort have been described in further detail elsewhere [ 21 , 22 ]. The current study is based on patients with stage I–III colon cancer from the initial cohort recruited between January 2013 and May 2014 [ 21 ] that did not undergo neoadjuvant treatment.…”

Section: Methodsmentioning

confidence: 99%

“…The protocol [ 18 ] and study cohort have been described in further detail elsewhere [ 21 , 22 ]. The current study is based on patients with stage I–III colon cancer from the initial cohort recruited between January 2013 and May 2014 [ 21 ] that did not undergo neoadjuvant treatment. Of 132 consecutive stage I–III colon cancers, 119 were included in the study.…”

Section: Methodsmentioning

confidence: 99%

“…Analysis of MSI has been described previously [ 31 , 32 ]. Briefly, FFPE blocks were selected by an experienced pathologist (DL) and 4 × 10 μm sections were cut at a microtome.…”

Section: Methodsmentioning

confidence: 99%

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A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment

Lea

Watson

Skaland

et al. 2021

Cancer Immunol Immunother

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Background In colon cancer, the location and density of tumor-infiltrating lymphocytes (TILs) can classify patients into low and high-risk groups for prognostication. While a commercially available ‘Immunoscore®’ exists, the incurred expenses and copyrights may prevent universal use. The aim of this study was to develop a robust and objective quantification method of TILs in colon cancer. Methods A consecutive, unselected series of specimens from patients with colon cancer were available for immunohistochemistry and assessment of TILs by automated digital pathology. CD3 + and CD8 + cells at the invasive margin and in tumor center were assessed on consecutive sections using automated digital pathology and image analysis software (Visiopharm®). An algorithm template for whole slide assessment, generated cell counts per square millimeters (cells/mm2), from which the immune score was calculated using distribution volumes. Furthermore, immune score was compared with clinical and histopathological characteristics to confirm its relevance. Results Based on the quantified TILs numbers by digital image analyses, patients were classified into low (n = 83, 69.7%), intermediate (n = 14, 11.8%) and high (n = 22, 18.5%) immune score groups. High immune score was associated with stage I–II tumors (p = 0.017) and a higher prevalence of microsatellite instable (MSI) tumors (p = 0.030). MSI tumors had a significantly higher numbers of CD3 + TILs in the invasive margin and CD8 + TILs in both tumor center and invasive margin, compared to microsatellite stable (MSS) tumors. Conclusion A digital template to quantify an easy-to-use immune score corresponds with clinicopathological features and MSI in colon cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment

Lea

Watson

Skaland

et al. 2021

Cancer Immunol Immunother

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“…Notably, one study previously reported an association with EMAST and CD8+ but not CD4+ T-cells infiltration in tumour [26]. In a previous report, a link between EMAST and older age and a frailer phenotype in patients with EMAST positive cancers was found [6]. These observations, pertinent to a cumulative increase in genetic abnormalities (e.g.…”

Section: Discussionmentioning

confidence: 91%

“…Prognostic data on EMAST is also scarce. In a previous study, we found that patients with EMAST+ were older, frailer and less likely to have recurrence from CRC [6].…”

Section: Introductionmentioning

confidence: 78%

Prevalence of PD-L1 expression is associated with EMAST, density of peritumoral T-cells and recurrence-free survival in operable non-metastatic colorectal cancer

Watson

Lea

Gudlaugsson

et al. 2020

Cancer Immunol Immunother

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Introduction Microsatellite instability (MSI) predict response to anti-PD1 immunotherapy in colorectal cancer (CRC). CRCs with MSI have higher infiltration of immune cells related to a better survival. Elevated Microsatellite Alterations at Tetranucleotides (EMAST) is a form of MSI but its association with PD-L1 expression and immune-cell infiltration is not known. Methods A consecutive, observational cohort of patients undergoing surgery for CRC. EMAST and clinicopathological characteristics were investigated against PD-L1, as well as CD3 and CD8 expression in the invasive margin or tumour centre (Immunoscore). Difference in survival between groups was assessed by log rank test. Results A total of 149 stage I-III CRCs patients, with a median follow up of 60.1 months. Patients with PD-L1+ tumours (7%) were older (median 79 vs 71 years, p = 0.045) and had EMAST+ cancers (OR 10.7, 95% CI 2.2-51.4, p = 0.001). Recurrence-free survival was longer in cancers with PD-L1+ immune cells (HR 0.35, 95% CI 0.16-0.76, p = 0.008, independent of EMAST) and high Immunoscore (HR 0.10, 95% CI 0.01-0.72, p = 0.022). Patients expressing PD-L1 in immune cells had longer disease-specific survival (HR 0.28, 95% CI 0.10-0.77, p = 0.014). Conclusions Higher Immunoscore (CD3/CD8 cells) and expression of tumour PD-L1 is found in CRCs with EMAST. Lymphocytic infiltrate and peritumoral PD-L1 expression have prognostic value in CRC.

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Prognostic significance of osteosarcopenia in older adults with colorectal cancer

Takano¹,

Kodera

Tsukihara³

et al. 2023

Annals of Gastroent Surgery

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Osteopenia and sarcopenia, features of the aging process, are recognized as major health problems in an aging society. This study investigated the prognostic impact of osteosarcopenia, the coexistence of osteopenia and sarcopenia, in older adults undergoing curative resection for colorectal cancer. MethodsWe retrospectively reviewed data of older adults aged 65-98 years who had undergone curative resection for colorectal cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images.Sarcopenia was evaluated by measuring the skeletal muscle cross-sectional area at the third lumbar vertebra level. Osteosarcopenia was de ned as the coexistence of osteopenia and sarcopenia. We explored the relationship of preoperative osteosarcopenia with the disease-free and overall survival after curative resection. ResultsAmong the 325 patients included, osteosarcopenia had signi cantly lower overall survival rates than those with osteopenia (P<0.01) or sarcopenia alone (P=0.036). In the multivariate analysis, male sex (P=0.045), C-reactive protein-to-albumin ratio (P<0.01), osteosarcopenia (P<0.01), pathological T4 stage (P=0.023), and pathological N1/N2 stage (P<0.01) were independent predictors of disease-free survival, while age (P<0.01), male sex (P=0.049), C-reactive protein-to-albumin ratio (P<0.01), osteosarcopenia (P<0.01), pathological T4 stage (P=0.036), pathological N1/N2 stage (P<0.01), and carbohydrate antigen 19-9 (P=0.041) were independent predictors of overall survival. ConclusionsOsteosarcopenia was a strong predictor of poor outcomes in older adults undergoing curative resection for colorectal cancer, suggesting an important role of osteosarcopenia in an aging society.

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Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST) in Colorectal Cancer is Associated with an Elderly, Frail Phenotype and Improved Recurrence-Free Survival

Cited by 15 publications

References 37 publications

A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment

A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment

Prevalence of PD-L1 expression is associated with EMAST, density of peritumoral T-cells and recurrence-free survival in operable non-metastatic colorectal cancer

Prognostic significance of osteosarcopenia in older adults with colorectal cancer

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