Relationship of the breast ductal carcinoma in situ immune microenvironment with clinico-pathological and genetic features

Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown. <br /><br />Experimental Design: We quantified tumour associated lymphocytes (TILs) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases respectively), some of which had copy number (n=55) and mutation data (n=20). <br /><br />Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range 0-90%). Most DCIS were negative for tumour cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high grade (p=0.002/0.035), ER-negative (p=0.02/0.02) and ERBB2 amplified tumours (p<0.001/0.048). Comedo necrosis was significantly positively associated with TILs (p<0.0001) but not PD-L1. The TILs score was significantly higher in cases with TP53 mutation (p=0.03) but not PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both p<0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels. <br /><br />Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumour copy number with the immune microenvironment, possibly by the immunoediting of the tumour.

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