Angiopoietin-Like Protein 4 and Insulin-Like Growth Factor-1 Expression in Invasive Breast Carcinoma in Young Women

Biomarker identification is imperative for invasive breast carcinoma, which is more aggressive and associated with higher mortality and worse prognosis in younger patients (<45 years) than in older patients (>50 years). The current study aimed to investigate angiopoietin-like protein 4 (ANGPTL4) and insulin-like growth factor-1 (IGF-1) protein expression in breast tissue from young patients with breast carcinoma. Immunohistochemical staining was applied in formalin-fixed, paraffin-embedded samples of breast carcinoma tissue from young patients aged <45 years at the time of diagnosis. Both proteins were expressed in the majority of cases. The highest frequency of positive ANGPTL4 and IGF-1 expression was observed in the luminal A subtype, whereas the HER2-overexpression subtype exhibited the lowest expression frequency for both proteins. There was no significant association between ANGPTL4 (p = 0.897) and IGF-1 (p = 0.091) expression and molecular subtypes of breast carcinoma. The histological grade was a significant predictor of ANGPTL4 expression (grade 1 vs. grade 3, adjusted odds ratio = 12.39, p = 0.040). Therefore, ANGPTL-4 and IGF-1 expressions are common in young breast carcinoma tissue. There is a potential use of them as biomarkers in breast carcinoma.

Correlation between the features of β1 and β3 integrin expression and lymphangitic metastatic spread in nonspecific invasive breast carcinoma based on tumor morphological heterogeneity

Objective. To study β1 and β3 integrin expression in nonspecific invasive breast carcinoma and to find the associations with parameters of tumor morphological heterogeneity and lymphatic dissemination.Material and Methods. Study group comprised 107 patients with breast cancer. Histological type of tumor corresponded to invasive carcinoma of a nonspecific type (invasive ductal carcinoma) in 100% of cases. Patients did not receive any preoperative treatment. In each case, we performed morphological examination of samples of primary tumor and axillary lymph nodes obtained at the surgical stage of treatment (radical mastectomy or sectoral resection of mammary gland with axillary lymphadenectomy). The parameters of β1 and β3 integrin expression in primary tumor tissue were assessed by immunohistochemistry.Results. The study demonstrated that an increase in the degree of malignancy of breast carcinoma was associated with a decrease in the incidence of positive expression of β1 integrin as well as with an increase in the incidence of positive expression of β3 integrin. Metastases in lymph nodes were significantly less frequently detected in the presence of positive expression of β1 integrin in the alveolar and solid structures compared with the cases of absent expression of the marker in similar structures (48%; χ2 = 3.5; p = 0.05 and 48%; χ2 = 4.8; p = 0.02, respectively). Lymphogenic metastasis were detected significantly more often in cases with positive expression of β3 integrin in discrete groups of cells compared with the cases where the expression of study marker in the described structures was absent (47 and 23%, respectively; χ2 = 5.1; p = 0.02).Conclusion. The results of work showed the presence of relationships between the morphological heterogeneity of the tumor and the parameters of β1 and β3 integrin expression in the parenchymal structures of the neoplasm. The study showed the association of described parameters with the frequency of lymphatic dissemination in patients with breast cancer. Obtained data expand and support previously known evidence and suggest the possibility of assessing the markers as potential prognostic factors predicting the course of cancer.

CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type

Background. Invasive breast carcinoma of no special type (IBC-NST) is the most widespread invasive carcinoma subtype causing primarily regional metastases of the lymphatic node (LNM). The capacity of CD44 variant exon 6 (CD44v6) expression as an LNM predictor biomarker in IBC-NST was explored. Methods. We conducted a cross-sectional research with 48 paraffin blocks containing IBC-NST primary tumors that were divided into two groups by LNM. The assessment has been carried out in terms of age, tumor size, tumor grade, lymphovascular invasion (LVI), and CD44v6 expression. The expression of CD44v6 was analyzed on the grounds of immunohistochemical (IHC) staining, while other data were taken from archives. Statistical analysis is carried out by univariate, multivariate, and AUROC. Results. CD44v6 exhibits a dominant expression in IBC-NST tumor cells. Univariate analysis revealed a significant association between CD44v6 and LNM status ( p = 0.001 ). Multiple logistic regression results showed that CD44v6 expression and LVI were significantly associated with LNM with OR 10.7 (95% CI: 2.43 to 47.08) and 6.22 (95% CI: 1.4 to 27.88), respectively. CD44v6 expression was able to discriminate against LNM with AUROC 0.863 ± 0.053 (95% CI: 0.759 to 0.967) at the H-score cut-off 133.889 (75% sensitivity and 83.3% specificity). Conclusion. CD44v6 expression and LVI are potential predictors of LNM in IBC-NST. The H-score cut-off of the CD44v6 expression can also be used as a threshold for classification in further investigation.

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases.