Abstract Background: Multicompartment tumor metabolism and metabolic coupling are markers of aggressive tumor behavior, clinically manifested as disease recurrence and progression. Loss of caveolin-1(CAV1) in stromal cells and upregulation of monocarboxylate transporters (MCTs), especially MCT1 and MCT4, in both stromal and cancer cells have been identified as playing an important role in the metabolic coupling necessary for release and uptake of metabolites. However, this phenomenon has only scarcely been described in ductal carcinoma in situ (DCIS) of the breast. The purpose of this study was to investigate the role of CAV1, MCT1, and MCT4 in DCIS carcinogenesis and its association with clinicopathologic factors. Materials and methods: CAV1, MCT1, and MCT4 expression was examined in 9 pairs of DCIS tissues and matched normal adjacent tissues at mRNA and protein levels by qRT-PCR, RNAscope in situ hybridization (ISH) and immunohistochemistry. Immunohistochemical staining of CAV1, MCT1, and MCT4 was done in 79 DCIS samples with known hormone receptor (HR) and human epidermal growth factor 2 (HER2) expression using tissue microarray. Results: CAV1 mRNA expression by qRT-PCR analysis was significantly decreased in DCIS tissues compared to their corresponding normal tissues. On the other hand, MCT1 and MCT4 mRNA expression in DCIS tissues were increased compared with corresponding normal tissues and the difference was statistically significant in MCT1. Compared with their corresponding normal tissues, DCIS tissues showed decreased stromal CAV1 mRNA and protein expression and increased epithelial MCT1 and MCT4 mRNA and protein expression by ISH and immunohistochemistry. Low stromal CAV1, high epithelial MCT1, and high epithelial MCT4 expressions were observed in 29 (36.7%), 51 (64.6%) and 15 (18.9%) cases with DCIS, respectively. Low stromal CAV1 expression was significantly associated with high nuclear grade (P < 0.05). High epithelial MCT4 expression was associated with larger tumor size and HER2 positivity (P < 0.05 and P < 0.05, respectively). Although not statistically significant, low stromal CAV1 and high epithelial MCT4 expression tended to be associated with recurrence of DCIS. No associations were observed between stromal CAV1 expression and epithelial MCT 1 or MCT4 expression. Conclusions: These results suggested that changes in CAV1, MCT1, and MCT4 are associated with carcinogenesis of DCIS, and further studies are needed for their clinical usefulness. Keywords: Ductal carcinoma in situ; CAV1; MCT1; MCT4; Metabolism Citation Format: Ji Shin Lee, Nah Ihm Kim, Min Ho Park. CAV1, MCT1, and MCT4 expression in ductal carcinoma in situ of the breast and its association with clinicopathologic features [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-12.