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

Abstract

Objective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.

Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.

Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.

Keywords: Argentine women; antigenic expression; breast cancer; prognostic factors; risk factors.

Figure 1

Photomicrographs of immunoperoxidase staining of primary ductal breast carcinoma samples (A–E) are shown. Staining with anti-MUC1 HMFG1 monoclonal antibodies (MAbs) (A), a mixed nonapical pattern of reaction with a strong intensity is observed; (B) a mixed reaction is shown (note the strong apical pattern); (C) staining with anti-MUC1 C595 MAb, a cytoplasmic and moderate reaction is depicted; (D) reaction obtained with anti-sialyl Lewis x MAb, a mixed reaction is shown; lumen content appears strongly stained; (E) the TF antigenic reaction shows a linear and apical pattern. Immunohistochemical reactions of metastatic lymphatic nodes (F–H) are depicted: (F) staining with anti-MUC1 HMFG1 MAb, a strong cytoplasmic reaction is shown; (G) the sialyl Lewis x cytoplasmic reaction is clearly visible in many metastatic cells and (H) staining obtained with anti-TF MAb, a cytoplasmic strong reaction is shown.

Figure 2

Relative percentage frequencies of staining obtained with the different anticarbohydrate antigens and MUC1 monoclonal antibodies according to tumor size. In all cases, a rising tendency is observed.

Figure 3

Apical expression frequencies of anti-MUC1 monoclonal antibodies according to histological grade. In all cases, apical expression decreases when histological differentiation grades increase.

Figure 4

Reactivity index according to disease stage. An increasing reactivity is observed in higher stages: (A) results obtained with anti-sialyl Lewis x monoclonal antibodies (MAbs) and (B) anti-TF MAbs.

Figure 5

Principal component analysis of reactivity indexes. Length of rays shows variable weights. Points represent each sample data. Patients aged <44 years appear grouped on the left of the graphic PC1(−), whereas middle-age groups remain mainly spread in PC2(+). Postmenopause and elder patient groups predominate on the right of the graphic (PC1(+),PC2(+) and PC1(+),PC2(−), respectively); I, II, and III indicate histological grades.

Figure 6

Photomicrographs of immunoperoxidase staining of benign breast diseases (A–D) and normal (E–H) are shown. Staining with anti-MUC1 HMFG1 monoclonal antibody (MAb), (A) an apical pattern of reaction with a strong intensity is observed in a non proliferative lesion; (E) normal mammary ducts are shown with an apical reactivity. Staining with anti-MUC1 C595 MAb, (B) a sample of an apocrine metaplasia is depicted; an apical mainly linear reaction is observed; (F) normal mammary gland sample showing a linear apical reaction. Expression of sialyl Lewis x (C) a strong linear staining in a fibroadenoma sample is shown and (G) a negative normal mammary gland sample is depicted. The TF antigenic reaction in (D) a fibroadenoma specimen is shown with a linear and apical pattern and in a (H) normal negative sample.