Prognosis Of Invasive Breast Carcinoma Research Articles

Vascular Endothelial Growth Factor Expression by Immunohistochemistry as a Possible Indicator of Prognosis in Invasive Breast Carcinoma of No Special Type.

Angiogenesis, the formation of new blood vessels from preexisting vascular network, is essential for tumor growth and spread. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor. To assess the expression of VEGF in invasive carcinoma of no special type and its correlation with all the known prognostic factors of breast carcinoma. Descriptive. Mastectomy specimens were studied noting the clinical details. The formalin-fixed tissues were subjected to routine processing and hematoxylin and eosin sections and studied extensively for all the histological prognostic factors. Representative sections from each case with the tumor were subjected to immunohistochemistry (IHC) staining with VEGF, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) antibodies. Descriptive statistics, Chi-square tests, contingency table analysis using SPSS for Windows. One hundred and twelve cases of invasive carcinoma of special type were studied to evaluate various clinicopathological parameters. The association of VEGF with clinicopathological parameters and all the known prognostic factors was studied to note its significance. VEGF overexpression was observed in 69% of the cases. It was noted that larger tumor size, higher histological grade, lymphovascular invasion, nodal involvement, tumor necrosis, high microvessel density, ER negativity, PR negativity, and HER2/neu positivity had a significant statistical association with VEGF overexpression. We conclude that incorporating VEGF as a biomarker along with the known factors into a prognostic index will not only help predict clinical outcome more accurately, but also determines the patient who can be benefited with combinational therapy including anti-VEGF factors.

CD8+ TILS Expression in Invasive Breast Carcinoma (No Special Type)

Invasive breast carcinoma (IBC) is the most cancer in women (24%) and the cause of cancer death in women worldwide. Based on data from globocan 2018 shows the incidence of breast cancer is around 2.08 million (11.6%) which is the second rank of all cancers after lung cancer with a mortality rate of 626.6 thousand (6.6%) which is also the most common cause of death in women. The basic role of the immune system in maintaining homeostasis by immunosurveillance and initiation of the inflammatory reactions that include coordination of innate and adaptive immune cells activation against tumor cells is one of the most important in the mechanism of tumor cell elimination. Prognosis of IBC were influenced by several factors, including tumor histology grade and Tumor Infiltrating Lymphocytes (TILs). Infiltration of lymphocytes in the tumor microenvironment/TILs through CD8+ T lymphocytes is known to be an important component of adaptive immunity that eliminates tumor cells. CD8+ T cells present tumor antigens on the surface of the major histocompatibility complex class I (MHC class I). Based on its importance in clinical application and it’s role in biological concepts, this study was conducted to determine the expression of CD8+ in Invasive Breast Carcinoma of No Special Type (IBC-NST) grades 1,2 and 3. Analytical study with a cross-sectional design on IBC-NST samples from 2017 until 2020 at the Laboratory of Anatomic Pathology, Faculty of Medicine, Hasanuddin University Makassar from May to August 2021. Immunoexpression data were analyzed to determine its relationship with grade. Eighty samples met the inclusion and exclusion criteria, there were 17 samples (21.3%) with grade 1, 32 samples (40%) with grade 2, and 31 samples (38.8%) with grade 3. In the high CD8+ TILs group, from a total of 27 samples, 10 samples with grade 1, 6 samples with grade 2, and as many as 11 samples with grade 3. In the low CD8+ TILs group, from a total of 53 samples, there were 7 samples with grade 1, 26 samples with grade 2, and 20 samples with grade 3. Based on the Chi-square test, p value = 0.017 (p <0.05). There is a significant difference in CD8+ TILS in Invasive Breast Carcinoma of No Special Type grade 1, grade 2 and grade 3.

High Pregnane X Receptor (PXR) Expression Is Correlated with Poor Prognosis in Invasive Breast Carcinoma.

Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells’ proliferative capacity, and overall disease-free patients’ survival. Additionally, the expression of PXR was examined on human breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expression was positively associated with nuclear grade (p = 0.0112) and histological grade of differentiation (p = 0.0305), as well as with tumor cells’ proliferative capacity (p = 0.0051), and negatively with luminal A subtype (p = 0.0295). Associations between high PXR expression, estrogen, and progesterone receptor negative status were also recorded (p = 0.0314 and p = 0.0208, respectively). High PXR expression was associated with shorter overall patients’ survival times (log-rank test, p = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients’ survival (Cox-regression analysis, p = 0.0082). PXR expression alterations were also noted in breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive breast carcinoma phenotype, being a strong and independent poor prognosticator.

The Prognostic Value of Retraction Clefts in Chinese Invasive Breast Cancer Patients.

Some studies reported the correlation between retraction clefts (RCs) and the clinicopathological features as well as prognosis in invasive breast carcinoma. However, limited number of investigations have been done and controversial results were reported. Larger population studies around the world might help to provide more accurate and comprehensive information. Thus, we examined the correlation between the extent of RCs and the clinicopathological features as well as the prognosis in 541 invasive breast carcinoma samples from Central China in this study. The statistical analyses were performed with the Pearson χ2 tests and univariate Cox proportional hazards regression assays. Compared with other studies, lower RCs occurrence rate (15.5%) was observed in Chinese breast cancer patients and opposite association between the presence of RCs and lymph nodes metastasis was identified, in which both progression free survival (PFS) and overall survival (OS) were improved with the presence of RCs in our study. Besides, despite some statistically significant associations between RCs and molecular subtypes, RCs and estrogen receptor status, the results were largely depending on the stratification methods. Generally, no convincing association was detected between the extent of RCs and the clinicopathological features or prognosis. In sum, the extent of RCs showed limited value as a prognostic predictor in invasive breast carcinoma patients from Central China.

CD 10: A Novel Stromal Marker in Pathogenesis and Prognosis of Invasive Breast Carcinoma

BACKGROUND: Breast carcinoma is the major cause of mortality and morbidity in Indian women. Though breast carcinoma arises from epithelial cells, stroma also plays a very important role in the pathogenesis of carcinoma breast which is assessed by the stromal marker CD 10. AIM : To study the stromal expression of CD 10 in carcinoma breast and find its relationship with other prognostic markers and study the role of stroma in pathogenesis of breast carcinoma. MATERIALS AND METHODS: 50 cases of breast cancer were included in the study. H & E slides were retrieved, reviewed and IHC was done with a panel of markers which included ER, PR, HER2/neu and CD 10. Stromal expression of CD 10 in invasive breast carcinoma was noted and analysed in correlation with other prognostic markers. RESULTS: Significances in the stromal CD 10 expression was calculated in regard to ER, PR & HER2/neu. Higher the tumour grade, more was the CD 10 stromal expression. CONCLUSION: As per the study, it is mandatory to include CD 10 stromal marker along with the panel of epithelial markers in invasive breast carcinoma. CD 10 contributes a potential target for development of novel therapies.

Correlation between the presence of androgenic receptors and molecular and histopathological variables in breast cancer

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objective: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Method: Retrospective cohort study, analyzing 119 cases of invasive non-metastatic BC, seen at a private clinic. Hormonal receptors were screened by immunohistochemical reaction, and AR were considered positive when present in at least 10% of cells, ER and PR from 1%. This finding was correlated with pathological staging, histological grade (HG), vascular-lymphatic invasion (VLI), estrogen (ER) and progesterone receptors (RP), HER2 and Ki 67. Results: Androgen receptors were positive in 80.6% of cases. In the assessment of pathological staging, of the 63 patients with stage I, 81% showed positive androgen receptors, while among the 28 patients with stage II, 75% had positive androgen receptors, and 88% of the 17 patients with stage III presented the positivity of the recipient. Regarding the histological parameters of the tumor, 16 patients had grade 1 tumors, 93.7% of them with positive androgen receptors, while among the 63 with grade 2 tumors 90.4% had androgen receptor positivity, and only 59, 3% of the 27 tumors evaluated as grade 3 had a positive androgen receptor. The vascular-lymphatic invasion was negative in 57 patients, 78.9% of the tumors with positive androgen receptor. Among the 56 tumors with positive vascular-lymphatic invasion, 85.7% had an androgen receptor positivity. In the immunohistochemical evaluation of tumors, among the 95 patients with positive estrogen receptors, 91.5% also had positive androgen receptor, which was positive in only 37.5% of the 24 patients with negative estrogen receptors. Of the 21 patients who had tumors with overexpressed HER, 85.7% also had positive androgen receptors, which were also positive in 86.4% of 96 without overexpression of HER2. In the evaluation of cell proliferation by the Ki67 antigen, among the 50 tumors with Ki67 &lt;20%, 94% had positive androgen receptors, while 83.7% were positive among the 49 tumors with Ki67 between 20 and 50% and only 35% positivity of androgen receptors in 17 tumors with Ki67&gt; 50%. Conclusions: AR positivity is associated with more differentiated hormone-dependent tumors with a lower proliferation rate.

Utility of PHH3 in Evaluation of Mitotic Index in Breast Carcinoma and Impact on Tumor Grade.

Background:Mitotic activity index is considered as the most important grading component to predict prognosis in invasive breast carcinoma. But it is believed that it is also the cause of discordance in grade estimation based on Bloom-Richardson system. Thus, reproducible methods such as immunohistochemistry (IHC) based analysis methods appears to be of great value in facilitating mitotic count. Materials and Methods:In the present study, we examined the utility of Phosphohistone H3 by IHC in various grades of breast carcinoma and compared it with traditional mitotic count by hematoxylin and eosin (H and E) staining and probable changes in tumor grading. Results:Total 90 cases of invasive breast carcinoma were evaluated. Mean mitotic count were 8.6 and 6.4/10HPF in IHC and HandE groups, respectively. Although , mean average count was higher by IHC method , good correlation was observed(R=0.914). Using PHH3 IHC, two out of 33 cases of grade I tumors were upgraded in to grade II and three cases of grade II were upgraded in to grade III. None of the tumors were down graded. Conclusion:Similar to some other previous studies, we found PHH3 a robust sensitive and practical marker for mitotic count in breast carcinoma. Especially it is helpful to identify the most proliferating area. However, further studies are required to confirm the superiority of this biomarker for including in grading system.

Extensive peritumoral retraction clefts and prognosis in invasive breast carcinomas of no specific type

Objective: To investigate the effect of extensive retraction clefts (RC, >20% of tumor volume) on prognosis in invasive breast carcinoma of no specific type (IBC-NST). Methods: A total of 2 184 cases of IBC-NST diagnosed at the Fourth Hospital of Hebei Medical University from January 2006 to December 2008 were collected. All the cases were diagnosed according to the latest guideline and standard. After excluding cases of shrinkage due to tissue fixation, 483 cases with RC were identified, and the clinical and pathological features were retrospectively analyzed. Results: Among the 483 cases, the mean tumor size was 2.0 cm (range 0.8 to 4.8 cm). Two hundred and thirty-two cases were moderately differentiated (48.0%), 97 were well differentiated (20.1%), 154 were poorly differentiated (31.9%); 382 (79.1%) cases were of stages Ⅰ and Ⅱ. A total of 177 cases (36.7%) had lymphatic invasion; nodal metastasis were found in 202 cases (41.8%). Extensive RC was found in 237 of 483 cases (49.1%). Follow-up information was available in 407 patients, and 46 died of breast cancer with survival time from 37 to 103 months. Multivariate analysis of extensive RC showed that tumor size, histological grade and nodal metastasis were risk factors of patients with IBC-NST (P<0.05). Lymphatic invasion and nodal metastasis were risk factors for extensive RCs in patients with IBC-NST (P<0.05). There was a high probability of lymph node metastasis in patients of extensive RC without lymphatic invasion, and the difference was statistically significant (P<0.05). Conclusions: Both lymphatic invasion and nodal metastasis are risk factors of extensive RC. The presence of extensive RC in IBC-NST patients is correlated with poor outcome. Tumors with lymphatic invasion are more likely to show extensive RC.

Expression of Ki-67 and Prognosis of Breast Invasive Carcinoma in Congolese Women

Breast invasive carcinoma is the most cancer in the world. In low resource countries, cancer are of poor prognosis for they are diagnosed at later stage. There is not a cancer registry in the Democratic Republic of Congo and studies on biomarkers are lacking. This study had the main purpose to determine the expression of Ki-67 and the prognosis of invasive breast carcinoma in Congolese women. Cross-sectional study of 86 women with invasive Breast Carcinoma were included in the Democratic Republic of Congo from Kinshasa (n=73) and Lubumbashi Cities (n= 13). Age at the time of diagnosis, tumor size, tumor necrosis, grade of tumor and proliferation index measured by Ki-67 were taken into account. Statistical analysis used SPSS program and Pearson Chi-square test. From 2014 to 2016, biopsies were collected from 86 Congolese patients to determine the expression of Ki-67 and the prognosis of invasive breast carcinoma. The proliferation marker was observed in 91.9%. K-i67 > 20% and > 30% were found respectively in 55.8% and in 33.7% of patients. The value of the Ki-67 was influenced by the tumor stage. The association between the size of the tumor and Ki-67 was statistically significant. The risk of tumor necrosis was 2.9 times in case of tumor with positive Ki-67. Ki-67 was positive in many patients younger than 45 years. However, the difference was not statistically significant. In patients with T3 and T4 tumors, the risk of positive Ki-67 was 7 times compared to those of T1 and T2 tumors. Patients with G3 tumors had 9 times the risk to have positive Ki-67 compared to those with G1 and G2 tumors. In conclusion, tumors in Congolese women are associated with higher proliferation index and poor prognosis for most of them are diagnosed at later stage. Chemotherapy can be justified for prior care in low resource countries and radical mastectomy should be encouraged.

Decorin Evokes Protracted Internalization and Degradation of the Epidermal Growth Factor Receptor via Caveolar Endocytosis

Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating its tyrosine kinase activity, thereby blocking the growth of a variety of transformed cells and tumor xenografts. In this study we provide evidence that decorin directly binds to the EGFR causing its dimerization, internalization, and ultimately its degradation. Using various pharmacological agents to disrupt clathrin-dependent and -independent endocytosis, we demonstrate that decorin evokes a protracted internalization of the EGFR primarily via caveolar-mediated endocytosis. In contrast to EGF, decorin targets the EGFR to caveolae, but not to early or recycling endosomes. Ultimately, however, both EGF- and decorin-induced pathways converge into late endosomes/lysosomes for final degradation. Thus, we have discovered a novel biological mechanism for decorin that could explain its anti-proliferative and anti-oncogenic mode of action.

Noninvasive carcinoma of the breast: angiogenesis and cell proliferation.

Angiogenesis and the cell proliferation index can predict the prognosis of invasive breast carcinoma; however, little is known of their roles in noninvasive tumor. To investigate the correlation of microvessel density and cell proliferation index with other histologic parameters (histologic type, nuclear grade, and mitotic count) in 65 cases of noninvasive carcinoma of the breast. Formalin-fixed, paraffin-embedded tissues from 65 cases of carcinoma in situ of the breast were immunostained with antibody against factor VIII antigen and proliferation-associated nuclear antigen MIB-1. The microvessel density was measured by counting the total number of microvessels around the carcinoma in situ per 10 low-power microscopic fields. The cell proliferation index was calculated by counting MIB-1-positive nuclei in 100 tumor cells. A chi2 test and Spearman rank correlation test were used for statistical analysis. The microvessel density and cell proliferation index of comedo-type, high-nuclear-grade ductal carcinomas in situ are significantly higher than those of either noncomedo type ductal carcinomas in situ or lobular carcinoma in situ (P <.001). Angiogenesis and the cell proliferation index are active biological processes and may be considered as markers to separate low- and high-risk patients with noninvasive breast carcinomas.

Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma.

Hypoxia and pH influence gene expression in tumours, and it is becoming increasingly clear that the pattern of genes expressed by a tumour determines its growth and survival characteristics. Hypoxia-inducible factor-1 (HIF-1) is a key mediator of the cellular response to hypoxia and high HIF-1 expression has been identified as a poor prognostic factor in tumours. Recently, we identified the tumour-associated carbonic anhydrases (CA), CA9 and CA12 as hypoxia-inducible in tumour cell lines. Furthermore, we identified CA IX to be a poor prognostic factor in breast cancer. The aim of this study was to assess the prognostic significance of CA XII. CA XII expression was studied by immunohistochemistry in a series of 103 cases of invasive breast cancer and any association with recognised prognostic factors or relation with the outcome was examined. CA XII expression was present in 77 out of 103 (75%) cases and was associated with lower grade (P=0.001), positive estrogen receptor status (P<0.001), and negative epidermal growth factor receptor status (P<0.001). Furthermore, although CA XII expression was associated with an absence of necrosis (P<0.001), expression of CA XII in some high-grade tumours was induced in regions directly adjacent to morphological necrosis. Additionally, using univariate analysis, CA XII positive tumours were associated with a lower relapse rate (P=0.04) and a better overall survival (P=0.01). In conclusion, CA XII expression is influenced both by factors related to differentiation and hypoxia in breast cancer in vivo and CA XII expression is associated with a better prognosis in an unselected series of invasive breast carcinoma patients.

Power Doppler sonography of breast masses: correlation of Doppler spectral parameters with tumor angiogenesis and histologic growth pattern.

The purpose of this study was to examine the relationship between spectral analysis on power Doppler sonography and microvessel density. Power Doppler sonography was performed in 71 patients with breast masses (36 invasive carcinomas and 35 benign lesions). Microvessel density was measured in surgical specimens from all breast carcinomas using anti-factor VIII-related antibody. Invasive carcinomas were divided into two groups according to their growth pattern (solid type, scirrhous type). The pulsatility index and resistive index were high in malignant tumors compared with those in benign lesions (P < 0.001). The maximum velocity had weak statistical significance (P < 0.05). Although the correlation of maximum velocity with microvessel density was strong in solid tumors (P < 0.001), the maximum intensity in scirrhous tumors had no correlation with microvessel density. In conclusion, solid tumors showed a tendency toward correlation of maximum velocity with microvessel density. High maximum velocity with high microvessel density suggests breast carcinoma and could be predictive of a poor prognosis in invasive breast carcinoma.

Immunohistochemical fibronectin staining pattern and prognosis in invasive breast carcinoma.

Fibronectin (FN) in 99 female patients with invasive breast carcinomas (IBCs) was studied by immunohistochemistry using a monoclonal antibody to human plasma FN. Sixty-five (65.7%) of 99 IBCs were FN-positive and 34 (34.3%) were FN-negative. The FN staining pattern was not correlated with patient characteristics, such as age, tumor size, nodal involvement and estrogen receptor status. Relapse-free survival (RFS) of patients with FN-positive tumors was significantly better than that of patients with FN-negative tumors. A multivariate analysis using the Cox proportional hazards model showed that the FN staining pattern was independently correlated with RFS as well as nodal status. The results show that FN staining pattern may be an independent prognostic factor in IBCs. It is suggested that patients with FN-negative tumors should be carefully followed up, even if axillary nodal invasion is absent.

Microvessel quantitation and prognosis in invasive breast carcinoma

The prognostic significance of microvessel quantitation in invasive breast carcinoma was analyzed in a study group that comprised 88 patients with axillary node-negative carcinoma and 32 patients with axillary node-positive carcinoma who had a minimum follow-up period of 9 years. Microvessels were identified by immunohistochemistry using antibodies to endothelial markers, including factor VIII-related antigen and blood group isoantigens (ABH). Factor VIII-related antigen staining provided more consistent results for microvessel quantitation than did staining for ABH isoantigens. The three most vascular areas within a tumor were selected, and the microvessels within a ×200 microscopic field of each area were counted by two investigators simultaneously. Node-positive carcinomas demonstrated significantly higher microvessel counts than did node-negative carcinomas (mean ± SD, 99 ± 42 and 73 ± 22, respectively; P < .001). In node-negative carcinomas, tumors from patients who experienced distant recurrence had higher microvessel counts than did tumors from patients who were disease-free (84 ± 19 and 70 ± 22; P = .01). Similarly, in patients with node-positive carcinoma, microvessel counts were considerably higher in tumors from patients who experienced distant recurrence than in patients who did not, although the difference did not reach statistical significance (113 ± 44 and 93 ± 34, respectively). Among patients with node-negative carcinoma, those with a microvessel count of less than 84 had a recurrence rate of 20% compared with 57% in patients with counts greater than 84 ( P = .003). Microvessel counts were independent of histologic parameters, ploidy status, and S-phase fraction but correlated with peritumoral vascular invasion. Both microvessel counts and vascular invasion were independent prognostic parameters by multivariate analysis. High vessel counts may represent increased tumor angiogenesis and are correlated with tumor aggressiveness. Microvessel quantitation may be an additional prognostic factor that, when used in conjunction with more established parameters, can help in appropriate patient management.