Tumour‐infiltrating lymphocytes in ductal carcinoma <i>in situ</i> (DCIS)—assessment with three different methodologies and correlation with Oncotype DX DCIS Score

Komforti, Miglena K.; Badve, Sunil; Harmon, Bryan; Lo, Yungtai; Fineberg, Susan

doi:10.1111/his.14181

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…Furthermore, Komforti et al revealed that the presence of touching-TILs (>5 touching TILs per DCIS duct) was significantly associated with high or intermediate Oncotype DCIS Score, hence worse outcomes in DCIS. 32 In several previous studies, the intrinsic immunological associations between dense TILs and worse prognosis in the DCIS population have been preliminarily described. In a study enrolling 138 patients with pure DCIS, both the fraction of the genome altered (FGA) and the number of telomeric imbalances were found to be positively associated with touching-TILs (both p < .001), which implies that the touching-TILs could be influenced by the antigens produced by copy number variation.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive significance of tumor infiltrating lymphocytes for ductal carcinoma in situ

Zheng

Che

et al. 2021

OncoImmunology

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This study aims to identify the density of TILs in ductal carcinoma in situ (DCIS) in terms of prognostic significance with recurrence and the benefit of whole breast irradiation (WBI). The clinicopathological data of DCIS patients from Jan 2009 to Dec 2016 who received breast-conserving surgery (BCS) were retrospectively reviewed. Cox regression analysis was used to confirm independent prognostic factors of ipsilateral breast tumor recurrence (IBTR). Kaplan-Meier method was utilized to analyze IBTR and values of WBI. Touching-tumor-infiltrating lymphocytes (TILs) were defined by TILs touching or within one lymphocyte cell thickness from the malignant ducts' basement membrane. In total, 129 patients were enrolled in this analysis with 98 patients who received WBI. After a median follow-up of 53.0 months, there were 16 IBTR events with five invasive IBTRs. Univariate and multivariate analyses showed that touching-TILs >5 were an independent prognostic factor for higher IBTR (HR = 6.17, 95%CI 1.95-19.56, p < .01). The whole cohort was classified into two subgroups: dense group (>5 touching-TILs per duct) and sparse group (≤5 touching-TILs per duct). Dense touching-TILs were associated with unfavorable biologic characteristics. The 5-y rate of IBTR between dense and sparse group was 29.0% versus 4.5% (p < .01). For the sparse group, WBI significantly reduced the rate of 5-y-IBTR risk from 13.2% to 1.7% (p = .02), but there was no benefit of WBI in the dense group. Touching-TILs density was heterogeneous in patients with DCIS. Sparse touching-TILs were associated with better prognosis and benefit from WBI. Dense touching-TILs not only were associated with a higher risk of IBTR but also lack of benefit from WBI.

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Section: Discussionmentioning

confidence: 99%

Prognostic and predictive significance of tumor infiltrating lymphocytes for ductal carcinoma in situ

Zheng

Che

et al. 2021

OncoImmunology

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“…The significance of TILs in predicting cancer outcome has been reported in many studies [ 8 , 16 , 17 ]. A proposal for a standardised method to evaluate TILs in solid tumours using HE-stained sections was introduced recently [ 9 , 10 ] and a good reproducibility in different cancer types has been reported [ 11 – 14 ].…”

Section: Discussionmentioning

confidence: 99%

Tumour-infiltrating lymphocytes in oropharyngeal cancer: a validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group

et al. 2022

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Background The evaluation of immune response can aid in prediction of cancer behaviour. Here, we assessed the prognostic significance of tumour-infiltrating lymphocytes (TILs) in oropharyngeal squamous cell carcinoma (OPSCC). Methods A total of 182 patients treated for OPSCC were included in this study. Assessment of TILs was conducted on tumour sections stained with standard haematoxylin and eosin (HE) staining. We used the scoring criteria proposed by the International Immuno-Oncology Biomarker Working Group. Results The multivariable analysis showed that TILs associated with disease-specific survival with a hazard ratio (HR) of 2.13 (95% CI 1.14–3.96; P = 0.017). Similarly, TILs associated significantly with overall survival with HR of 1.87 (95% CI 1.11–3.13; P = 0.018). In a sub-analysis of HPV-positive and HPV-negative cases separately, TILs showed a significant prognostic value in both groups (P < 0.05). Conclusion The evaluation of TILs as proposed by the International Immuno-Oncology Biomarker Working Group is a simple and promising method in prediction of survival of OPSCC. It is easily applicable and after further validation can be implemented in the routine pathological report as a basic immune parameter.

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“…In a study of 198 cases with recurrence follow-up reported, a significant association between circumferential TILs and worse disease-free survival [ 40 ]. Recently, Komforti et al [ 24 ] assessed the pattern of TILs in a series of 97 cases by three different methodologies [ 20 , 23 , 41 ]. Stromal TILs showed the lowest concordance rate, followed by touching TILs by all pathologists.…”

Section: Discussionmentioning

confidence: 99%

“…The observers were blinded to the clinical data. The amount and distribution of TILs were assessed using the previously described methodologies, including the estimation of stromal TILs, the estimation of TILs touching DCIS ducts, and the assessment of circumferential TILs and presence or absence of hotspots [ 23 , 24 ]. TILs associated with areas of necrosis, prior biopsy, and crush artefacts were excluded from the analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Their analysis showed that touching TILs in DCIS was an independent prognostic variable in DCIS [ 23 ]. We adopted these methods to analyze a series of DCIS cases from four institutions and found that the presence of TILs was associated with incidences of recurrence [ 24 ]. Recent data indicates immunological differences in invasive cancer in Asians, but less is known about DCIS [ 25 , 26 ] The current study focuses on the assessment of TILs in a multi-national and multi-ethnic cohort to seek to understand the impact, if any, of TILs on the likelihood of development of invasive ipsilateral breast cancer events.…”

Section: Introductionmentioning

confidence: 99%

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Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast

Badve

Cho²,

Lu³

et al. 2022

Cancers

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Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.

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Tumour‐infiltrating lymphocytes in ductal carcinoma in situ (DCIS)—assessment with three different methodologies and correlation with Oncotype DX DCIS Score

Cited by 7 publications

References 29 publications

Prognostic and predictive significance of tumor infiltrating lymphocytes for ductal carcinoma in situ

Prognostic and predictive significance of tumor infiltrating lymphocytes for ductal carcinoma in situ

Tumour-infiltrating lymphocytes in oropharyngeal cancer: a validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group

Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast

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