Comparative Immunohistochemical Study of MUC1 and Carbohydrate Antigens in Breast Benign Disease and Normal Mammary Gland

Abstract

The aim was to compare the expression of MUC1 and carbohydrate antigens in 124 tissue samples; 42 fibroadenoma (FA), 23 nonproliferative benign diseases (NPF), 25 usual epithelial hyperplasia (UEH), 7 atypical ductal hyperplasia (ADH), and 27 breast normal tissues. An immunohistochemical approach was adopted, using the following antibodies: reactive with MUC1 variable number of tandem repeats (C595, HMFG2, and SM3 monoclonal antibodies), anti-MUC1-cytoplasmic tail polyclonal antibody (CT33), and anti-carbohydrate antigens (sialyl Lewis x, Lewis x, Lewis y, Tn, and Thomsen-Friedenreich epitopes). Positive area of reaction, intensity, and pattern of expression were considered. A reactivity index was calculated as intensity (I) x 100+percentage of positive area (A). Statistical analysis comprised frequency analysis, P < 0.05, analysis of variance, and multiple correlation with principal component analysis. All samples expressed MUC1, detected by at least one anti-MUC1 antibody whereas Lewis x was the carbohydrate antigen most frequently found in all groups whereas variable number of tandem repeats MUC1 and Lewis x showed the highest correlation: 93% of normal samples, 62.5% of NPF, 87% of FA, 85% of UEH, and finally 80% of ADH. Although principal component analysis using reactivity indexes explained only 39% of data variability, normal samples appeared grouped and separated from benign breast diseases, which remained spread. Thomsen-Friedenreich was the only antigen that showed an increased tendency for positive expression and intensity from NPF through FA, UEH to ADH, whereas it was not detected in normals. With respect to the pattern of expression, an apical pattern was predominantly found in all the groups.

Immunohistochemical evidence of Muc1 expression during rat embryonic development

“…4,7,24,25 In fact, MUC1 was the first mucin to be cloned, initially from mammary carcinomas 26 and subsequently from other tissues. 27 Considering that this research was developed in order to study Muc1 expression from the first stages of rat embryonic development up to birth, we included organs that express Muc1 in adults and that may be identified during the developmental process.…”

Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

“…A reactivity index (RI) was calculated as intensity (I) × 100 + percentage of positive area (A). 26 Normality of variables was tested by Shapiro Wilk's, and data were normalized when necessary.…”

“…In order to analyze in more depth the antigenic expression, RI was calculated as intensity (I) × 100 + percentage of positive area (A). 26 According to anti-MUC1 MAb in relation to disease stage, for HMFG1, MAb RI and Stage I results were 355 ± 155, Stage II 386 ± 113, Stage III 389 ± 98, and Stage IV 480 ± 71. A raise tendency was detected but with no statistical significance (Tukey HSD; P = 0.067) ( Figure 3 Percentage of positive responses detected with all MAbs increased according to tumor size increment (Figure 2), with statistically significant C595 and SM3 MAbs reactivity (P , 0.040).…”

Transmembrane mucins as novel therapeutic targets

“…Moreover, complex peripheral O -linked oligosaccharide antigens can also form from further glycosylation of the core 2 antigen, for example, the variations of Lewis and Sialyl–Lewis antigens [19,107–109]. Clinicians and researchers have taken advantage of these antigens, using monoclonal antibodies specific towards these unique carbohydrate targets and exposed protein core to distinguish cancerous from healthy tissue [36,110–112]. Interestingly, the overexpression of sialyltransferases and subsequential increased sialylation is in itself believed to be important in the progression of many types of cancer [113–120]; however, a mechanism has not been proposed.…”