MUC1 is expressed at high frequency in early-stage basal-like triple-negative breast cancer

Abstract

Triple-negative breast cancer comprises 10% to 15% of newly diagnosed breast cancer and lacks expression of the estrogen, progesterone, and human epidermal growth factor receptor 2/neu receptors. Many such tumors are basal like, a molecular intrinsic subtype of breast cancer associated with poor clinical outcomes. Patients with early-stage basal-like triple-negative breast cancer are at a high risk for relapse and may, therefore, benefit from novel therapies, including immunotherapy. MUC1 is a tumor antigen expressed on adenocarcinomas and represents an ideal target for MUC1-based vaccination. We evaluated 52 cases of early-stage basal-like triple-negative breast cancer for MUC1 expression by immunohistochemistry. The intensity of staining was graded according to the intensity (negative [0], positive [1], or strongly positive [2]) and percentage (0%-100%) of tumor cells staining for MUC1. An overall score of 0 to 2.0 was calculated for each case by multiplying the intensity of staining by the percentage of tumor cells staining positively. Four staining patterns for MUC1 were identified: apical, cytoplasmic, membranous, and combination. Of the 52 cases of basal-like triple-negative breast cancers, 49 (94%) were positive for MUC1 expression. The mean score was 0.90 (range, 0-1.9). Cases were evenly distributed over this range, where most (67%) exhibited moderate to strong MUC1 expression (score, 0.5-1.90), 27% demonstrated weak MUC1 expression, and 6% lacked MUC1 expression. There was a significant difference in MUC1 score and percent MUC1+ cells in favor of the combination pattern. This study indicates that a large proportion of early-stage basal-like triple-negative breast cancer expresses MUC1 and provides a rationale for MUC1-based immunotherapy in this high-risk patient cohort.

Keywords: Basal-like; Mucin; Triple-negative breast cancer.

Fig. 1

(A) H&E section and (B) MUC1 immunostained sections of a poorly differentiated triple negative breast carcinoma, both 200× magnification. The overall MUC1 score in this case was 1.6 (2 for intensity, 80% of cells staining).

Fig. 2

Representative photomicrographs of different patterns of MUC1 staining in TNBC specimens. (A) apical; (B) cytoplasmic; (C) membranous; (D) combination (in this case, apical and cytoplasmic).

Fig. 3

MUC1 intensity score according to staining pattern. There was no significant difference of MUC1 intensity among 4 staining sites (p = 0.237).

Fig. 4

Box plot staining analyses according to (A) percent MUC1 and (B) MUC1 score. Red bar = median; Green box = 25^th to 75^th percentiles; Bars = entire range. (A) There was a significant difference of percent MUC1 among 4 staining sites (p = 0.003). By Tukey's pair-wise comparison procedure, the difference was from apical and combination (p < 0.05) as well as from cytoplasmic and combination (p < 0.05). (B) There was a significant difference of MUC1 score among 4 staining sites (p = 0.006). By Tukey's pair-wise comparison procedure, the difference was from apical and combination (p < 0.05) as well as from cytoplasmic and combination (p < 0.05).

Fig. 5

Kaplan-Meier estimation of survivor distributions: (A) Overall survival (OS) with 95% confidence interval; (B) Disease-free survival (DFS) with 95% confidence interval; (C) DFS stratified by staining site.

Fig. 5

Kaplan-Meier estimation of survivor distributions: (A) Overall survival (OS) with 95% confidence interval; (B) Disease-free survival (DFS) with 95% confidence interval; (C) DFS stratified by staining site.