Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups – Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades.Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Correlation of clinicopathology and ipsilateral axillary lymph node metastasis with Ki-67 expression in non-special invasive breast cancer / 西安交通大学学报(医学版)

【Objective】 To investigate the clinicopathological characteristics of non-specific invasive breast cancer (IBC-NST) and the relationship between ipsilateral axillary lymph node metastasis and Ki-67 expression. 【Methods】 A total of 101 patients with IBC-NST were retrospectivily recruited and divided into two groups with high expression of Ki-67 (70cases) and low expression of Ki-67 (31cases). The χ2 test and Kruskal-Wallis H test were used to compare the clinical and pathological characteristics and other count data of patients between the groups. The comparison of ultrasound diagnosis of ipsilateral axillary lymph node metastasis and pathological results was calculated using correlation values such as sensitivity and specificity. The correlation between ipsilateral axillary lymph node metastasis and Ki-67 expression was analyzed with Spearman correlation analysis. 【Results】 In different Ki-67 expression groups, the size of tumor mass, histological grade of breast cancer, and clinical stage were statistically different between Ki-67 expression groups (P<0.05). The positive expression rate of tumor mass ≥2 cm (58.57%), histological grade Ⅲ (32.86%), clinical stages Ⅲ (34.29%) and Ⅳ (5.71%) was higher in the Ki-67 high expression group; ipsilateral axillary lymph node metastasis and Ki-67 high expression were positively correlated (r=0.393, P<0.05). 【Conclusion】 In IBC-NST cases, the tumor mass ≥ 2 cm, histological grade Ⅲ, clinical stage Ⅲ, and Ⅳ are correlated with the high expression of Ki-67. At the same time, ipsilateral axillary lymph node metastasis and Ki-67 high expression are positively correlated, which provides reference for IBC-NST proliferation assessment and clinical intervention.

Multi-omics approaches identify

Autophagy is a critical cellular homeostatic mechanism, and its dysfunction is linked to invasive breast carcinoma (BRCA). Recently, several omics methods have been applied to explore autophagic regulators in BRCA; however, more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered. Thus, we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA, including gene expression (EXP), DNA methylation (MET) and copy number alterations (CNAs) from The Cancer Genome Atlas (TCGA). Newly identified candidate genes, such as

Androgen receptor expression in triple negative breast carcinoma and its association with the clinicopathological parameters

@#Introduction: Androgen receptor (AR) is the most frequently expressed biomarker in all subtypes of breast carcinoma. Triple negative breast carcinoma (TNBC) is breast carcinoma that lacks oestrogen and progesterone receptors immunoexpression as well as absence of HER2/neu gene amplification. This makes targeted therapy not feasible in this cancer and hence has poorer prognosis. Detecting AR expression could be another milestone in the management of TNBC, as AR is a prognostic, predictive marker and potential index for targeted treatment. This study aimed to assess expression of AR in TNBC by immunohistochemistry and its association with clinicopathological parameters. Methods: We analysed the expression of AR in 97 TNBC cases from Penang General Hospital for a period of 3 years (2014 to 2017). Androgen receptor immunoreactivity was considered positive if > 1% of tumour cells nuclei were stained irrespective of staining intensity. Results: The prevalence of AR expression in TNBC was 31% (30/97), with the proportion of AR-positive tumour cells ranged from 1% to 90%. These include 23 invasive carcinomas, no special type (NST) and 7 other invasive carcinoma subtypes (papillary, lobular, clear cell and medullary carcinomas). Sixty-seven cases (69%) that showed AR immunonegativity were invasive carcinomas, NST (n=60), clear cell carcinoma (n=1) and metaplastic carcinoma (n=6). Androgen receptor immunoexpression was inversely correlated with tumour grade (p=0.016), but not the tumour stage, tumour size and nodal status. Conclusion: AR is expressed in about one-third of TNBC and loss of AR immunoexpression does not predict adverse clinical outcomes. Larger cohorts for better characterisation of the role of AR immunoexpression in TNBC are warranted.

A study on stromal CD10 expression in invasive breast carcinoma

Introduction: Breast cancer is one of the most common cancers among Indian women. Although breast cancer is an epithelial malignancy, stroma plays a key role in modulating tumor invasion and metastasis. Stromal markers are now emerging as novel markers in assessing the prognosis of invasive breast cancer and have not been studied extensively till date. Aim and objectives: To estimate the frequency of expression of stromal CD10 in invasive breast carcinomas, to assess prognostic significance of stromal CD10 expression and its correlation with other clinicopathological factors like age, menopausal status, tumor size, grade and lymph node status. Materials and methods: A total of 59 cases of breast cancer were included in the study. Representative sections were taken and hematoxylin and eosin staining was done. Immunohistochemistry was performed with CD10. Stromal expression of CD10 (>10% stromal positivity was considered positive) in invasive breast carcinoma was noted and was statistically analyzed with different known prognostic markers of breast carcinoma. Results: Stromal expression of CD10 was found to be significantly associated with increasing tumor size (P = 0.03), increasing tumour grade (P =0.001), worsening prognosis (P = 0.002) and lymph node status (0.0005). No correlation was found between CD10 over expression and age, menopausal status. Conclusion: Tumor grade is a major prognostic indicator of breast carcinoma. Tumor size and nodal status on the other hand, are important determinants of tumor stage. Therefore, our findings concerning the positive correlations between stromal CD10 expression and tumor grade, tumor size, B. V. Anuradha Devi, S. Chandra Sekhar, C. Saritha, S. Sanhya Anil, H. Sandhya Rani. A study on stromal CD10 expression in invasive breast carcinoma. IAIM, 2016; 3(6): 142-147. Page 143 and nodal status suggest a strong effect of stromal CD10 expression on aggressive behavior of breast carcinoma and introduce this marker as a potential prognostic determinant in breast cancer.

Mast Cell and Macrophage Counts and Microvessel Density in Invasive Breast Carcinoma-Comparison Analysis with Clinicopathological Parameters / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the clinicopathological significance of the microvessel density and macrophage and mast cell counts in invasive breast carcinomas. MATERIALS AND METHODS: 45 invasive breast carcinomas were immunohistochemically stained with the endothelial antigen, CD34, and macrophage marker, CD68. 0.1% toluidine blue was used to highlight mast cells. The microvessel and mast cell counts were performed at x200 magnification and the macrophages at x400 magnification. RESULTS: With the 45 invasive breast carcinomas, there were no statistically significant associations between the mast cell, macrophage and microvessel counts and the tumor size and lymph node status. ER and PR negative mast cells infiltrated more than in cases of positive stati, with statistical significance (p-value=0.010 and 0.005, respectively). The macrophage counts were negatively correlated with the PR status (p-value=0.030). With respect to the c-erbB-2 status, there was no significance correlation with the mast cell, macrophage and microvessel counts. The mast cell counts showed significantly positive correlation with the microvessel counts in the invasive breast carcinomas (p-value=0.015). In a comparison of the macrophage counts with the microvessel counts, a positive tendency for both parameters, but without statistical significance (p-value=0.310). CONCLUSION: Increasing numbers of mast cells and macrophages were recruited in invasive breast carcinomas, which contribute to angiogenesis. The microvessel density in invasive breast carcinomas had no statistically significant association with the tumor size, lymph node status, and histological grade, presence of DCIS component, estrogen/progesterone receptor status and cerbB-2 status. The evaluation of angiogenesis using these methods is not thought to provide an independent clinicopathological factor in invasive breast carcinomas.

Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast

The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.

Correlation of Heregulin mRNA and Her-2/neu Protein Expression with Node Metastasis and DNA Ploidy Pattern in Human Invasive Breast Carcinoma

The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.

Microvessel Quantitation and Assessment of its Utility by CD34 Staining in Invasive Breast Carcinoma

Tumor angiogenesis, the development of new blood vessels by tumor, is a widely observed phenomenon associated with the growth of human solid tumors. To investigate how tumor angiogenesis correlates with other prognostic features i.e. menopause status, tumor size, lymph node metastasis, mitosis, angioinvasion, estrogen receptor (ER), p53 protein expression, histologic grade and clinical stage, we counted microvessels by immunohistochemistry using antibody for CD34 antigen in 56 cases of invasive breast carcinoma (27 with and 29 without axillary lymph node metastases) and 20 cases of non-inflammatory benign breast lesion. CD34 antigen is expressed on the surface of hematopoietic progenitor cells and more sensitively expressed than factor VIII in vascular endothelial cells. Microvessel count (MVC) was performed at a single hot field of 200x magnification (0.74 mm2 per field). The results are summarized as follows; 1) The mean MVC of invasive carcinoma and benign breast lesion were 92.0+/-54.4 (range, 7-237) and 20.7+/-16.6 (range, 4-73), respectively (p0.05), MVC had a tendency to increase in tumors with axillary LN metastasis or without ER expression. 3) Without correlation with MVC, ER (+), angioinvasion (-) and higher histologic grade correlate to significantly higher mitosis count (p<0.0005). Also, angioinvasion correlate to a significantly higher histologic grade (p<0.05). In conclusion, angiogenesis is related to tumorigenesis, but MVC may not be related to other clinicopathologic factors.