Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors

Background. Study of tumor molecular characteristics is necessary to understand both the risk of breast cancer recurrence and the response to therapy.Aims. To evaluate p53, HoxD10, and E-cadherin status in breast cancer and to correlate with histological grade and other prognostic factors.Material and Methods. The study was conducted in 60 cases of invasive ductal carcinoma NOS with 20 cases belonging to each grade and evaluation of p53 was done by IHC and that of HoxD10 and E Cadherin status by PCR and correlation was done with histological grade and other prognostic factors.Result. p53 expression was seen in 71.67% (43/60) of the tumors. HoxD10 gene was downregulated in 46.67% (28/60) of the tumors. p53 overexpression and lower HoxD10 mRNA levels showed statistically significant association higher histological grade of the tumor (P<0.05). CDH1 gene mutation was seen in 60% (15/25) of the tumors. No significant association was found between p53 expression, HoxD10 gene, CDH1 gene mutation, and other prognostic factors.Conclusion. p53 over expression and lower HoxD10 mRNA levels were found to be significantly associated with higher grade tumours. This suggests that p53 and HoxD10 gene play an important tumor suppressor role and the loss of which results in breast cancer progression.

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Characteristics of medullary breast carcinoma compared with invasive ductal carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.20 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 20-20

Author(s):

Inhye Park ◽

Jiyoung Kim ◽

Se-Kyung Lee ◽

Min-Young Choi ◽

Su Yeon Bae ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Invasive Ductal Carcinoma ◽

Tumor Size ◽

Ductal Carcinoma ◽

Histological Grade ◽

Clinicopathologic Features ◽

Node Metastasis

20 Background: Medullary carcinoma (MC) represents a rare breast cancer subtype associated with a rather favorable prognosis compared with invasive ductal carcinoma (IDC). It is characterized by the high-grade structure and lymphocytic infiltration, hemorrhagic necrosis. The purpose of this study is to compare the clinicopathologic characteristics and outcome of MC to IDC. Methods: We retrospectively reviewed the medical records of patients with invasive breast cancer managed with operation at Samsung Medical Center in Korea from January 1995 to June 2010 except patients diagnosed with ductal carcinoma in situ, patients with distant metastasis at diagnosis or neoadjuvant chemotherapy. 52 cases were identified with MC; 5,716 patients with IDC. The clinicopathologic features, disease-free survival (DFS) and overall survival (OS) for patients with MC were compared with those of the IDC patients. Results: The medullary group presented at younger age (43.9 ± 8.8 vs 47.7 ± 9.9, p=0.006). Also the medullary group was significantly associated with higher histological grade (poor; 80.0 vs 38.3%, p=0.003) and nuclear grade (grade3; 82.8 vs 41.7%, p<0.001) as well as negative ER (84.8 vs 31.0%, p<0.001) and PR status (91.3 vs 38.8%, p<0.001) regarded as poor prognostic factors. But lymphatic invasion was rare (0.0 vs 29.8%, p<0.001) and N stage was low (N0; 86.5 vs 58.4%, p<0.001). The DFS and OS were not significantly different between the medullary and IDC groups. (5-yr DFS : 88.0 vs 89.2 %, p=0.917, 5-yr OS : 94.4 vs 93.4%, p=0.502) In multivariable analysis, factors associated with DFS and OS included nuclear grade, histological grade, tumor size, lymph node metastasis, ER/PR/C-erbB2 status, chemotherapy and hormone therapy. When adjusting for other factors, histological type itself did not show significant difference from IDC in DFS and OS. Conclusions: Despite MC present specific clinicopathologic features, prognosis is not different from IDC and determined by already known prognostic factors such as tumor size, lymph node metastasis. Therefore, the patients with MC also need aggressive treatment like IDC.

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p53 expression in human breast cancer related to survival and prognostic factors: An immunohistochemical study

The Journal of Pathology ◽

10.1002/path.1711640113 ◽

1991 ◽

Vol 164 (1) ◽

pp. 75-81 ◽

Cited By ~ 136

Author(s):

J. L. Ostrowski ◽

A. Sawan ◽

L. Henry ◽

C. Wright ◽

J. A. Henry ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Human Breast Cancer ◽

Immunohistochemical Study ◽

Human Breast ◽

P53 Expression

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Prognostic Factors in the Initial Response to Therapy by Patients With Advanced Breast Cancer 2

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/60.4.731 ◽

1978 ◽

Vol 60 (4) ◽

pp. 731-736 ◽

Cited By ~ 33

Author(s):

Stephen L. George ◽

Barth Hoogstraten

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Advanced Breast Cancer ◽

Initial Response ◽

Response To Therapy ◽

Advanced Breast

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Igf-Ii Mrna Expression in Breast Cancer: Predictive Value and Relationship to Other Prognostic Factors

The International Journal of Biological Markers ◽

10.1177/172460081002500305 ◽

2010 ◽

Vol 25 (3) ◽

pp. 150-156 ◽

Cited By ~ 6

Author(s):

Emilio Fiore ◽

Daniela Campani ◽

Ilaria Muller ◽

Valentina Belardi ◽

Elisa Giustarini ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Mrna Expression ◽

Ductal Carcinoma ◽

P53 Protein ◽

Independent Predictive Factor ◽

Ki 67 ◽

P53 Expression ◽

Predictive Parameters ◽

The Difference

Purpose Insulin-like growth factor-II (IGF-II) is an important regulator of tumor growth in breast cancer. In this study we have examined the prognostic value of IGF-II mRNA expression in breast cancer and its relationship to other predictive parameters. Patients Sixty-eight women with infiltrating ductal carcinoma were given the same treatments including mastectomy and antitumoral therapies and followed up for 5 years. Results The overall 5-year survival rate was 73.5% (55/68). IGF-II mRNA was expressed in 33/64 patients (51.6%) and had no significant impact on survival. The expression of estrogen receptor (ER) and progesterone receptor (PgR) did not significantly affect the 5-year survival, but in the presence of an IGF-II mRNA signal, the survival of ER- and PgR-negative patients (n=9) was lower than that of ER- and PgR-positive patients (n=15), although the difference was not significant. The 5-year survival was not significantly different between Ki-67-positive and negative patients, but in the IGF-II positive group Ki-67-positive patients (n=7) had a significantly poorer prognosis than Ki-67-negative patients (n=26). The expression of p53 protein was associated with a poorer prognosis: 6/11 (54.5%) p53-positive patients died in the first 26 months of follow-up and 5 of these 6 patients (83.3%) also had positive IGF-II mRNA expression. Conclusions IGF-II mRNA expression per se is not an independent predictive factor in breast cancer but may be a marker of poor prognosis when associated with other prognostic factors such as Ki-67 index and p53 expression.

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Reduced MLH1 Expression in Breast Tumors After Primary Chemotherapy Predicts Disease-Free Survival

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.1.87 ◽

2000 ◽

Vol 18 (1) ◽

pp. 87-87 ◽

Cited By ~ 60

Author(s):

H.J. Mackay ◽

D. Cameron ◽

M. Rahilly ◽

M.J. Mackean ◽

J. Paul ◽

...

Keyword(s):

Breast Cancer ◽

Locally Advanced ◽

Disease Free Survival ◽

Response To Therapy ◽

Primary Chemotherapy ◽

Independent Predictive Factor ◽

P53 Expression ◽

Free Survival ◽

Response To Chemotherapy ◽

Disease Free

PURPOSE: Loss of function or expression of the mismatch repair protein MLH1 and the tumor suppressor protein p53 have been implicated in acquired resistance to anticancer drugs. We have compared the expression of MLH1 and p53 in tumors from women with clinically node-positive breast cancer before and after primary (neoadjuvant) chemotherapy. Further, we have assessed the value of these markers as predictors of response to therapy by correlation with disease-free survival. PATIENTS AND METHODS: Immunohistochemistry scores of MLH1 and p53 expression were made on 36 tru-cut prechemotherapy biopsies and 29 paired postchemotherapy tumor samples. The significance of the change in scores and their correlation with disease-free survival were evaluated by the Wilcoxon signed rank sum test and Cox proportional hazards regression analysis, respectively. RESULTS: Primary chemotherapy results in a significant reduction in the percent of cells expressing MLH1 (P = .010). This change in MLH1 expression after chemotherapy is strongly associated with poor disease-free survival (P = .0025). Expression of p53 was not significantly altered by chemotherapy. Neither MLH1 nor p53 expression before chemotherapy predicted disease-free survival or tumor response to chemotherapy. Low MLH1 expression after chemotherapy was an independent predictor of poor disease-free survival on multivariate Cox analysis when considered with other clinicopathologic prognostic factors. CONCLUSION: Tumor cells that have reduced MLH1 expression seem to have a survival advantage during combined chemotherapy of locally advanced breast cancers, which supports the hypothesis that loss of MLH1 has a role in drug resistance. MLH1 expression after chemotherapy is an independent predictive factor for poor disease-free survival and may, therefore, define a group of patients with drug-resistant breast cancer.

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The role of the AR/ER ratio in ER-positive breast cancer patients

Endocrine Related Cancer ◽

10.1530/erc-17-0417 ◽

2018 ◽

Vol 25 (3) ◽

pp. 163-172 ◽

Cited By ~ 15

Author(s):

Nelson Rangel ◽

Milena Rondon-Lagos ◽

Laura Annaratone ◽

Simona Osella-Abate ◽

Jasna Metovic ◽

...

Keyword(s):

Breast Cancer ◽

Histological Grade ◽

Molecular Characteristics ◽

Prognostic Impact ◽

Breast Cancer Patients ◽

Disease Free Interval ◽

Hazard Ratios ◽

Er Positive ◽

Independent Marker

The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, bothP ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours.

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Intrinsic Subtypes and Androgen Receptor Gene Expression in Primary Breast Cancer. A Meta-Analysis

Biology ◽

10.3390/biology10090834 ◽

2021 ◽

Vol 10 (9) ◽

pp. 834

Author(s):

Paola Cruz-Tapias ◽

Wilson Rubiano ◽

Milena Rondón-Lagos ◽

Victoria-E. Villegas ◽

Nelson Rangel

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Androgen Receptor ◽

Large Scale ◽

Histological Grade ◽

Meta Analysis ◽

Receptor Gene ◽

Mrna Level ◽

Mrna Levels ◽

Luminal A

The androgen receptor (AR) is frequently expressed in breast cancer (BC), but its association with clinical and biological parameters of BC patients remains unclear. Here, we investigated the association of AR gene expression according to intrinsic BC subtypes by meta-analysis of large-scale microarray transcriptomic datasets. Sixty-two datasets including 10315 BC patients were used in the meta-analyses. Interestingly, AR mRNA level is significantly increased in patients categorized with less aggressive intrinsic molecular subtypes including, Luminal A compared to Basal-like (standardized mean difference, SMD: 2.12; 95% confidence interval, CI: 1.88 to 2.35; p < 0.001) or when comparing Luminal B to Basal-like (SMD: 1.53; CI: 1.33 to 1.72; p < 0.001). The same trend was observed when analyses were performed using immunohistochemistry-based surrogate subtypes. Consistently, the AR mRNA expression was higher in patients with low histological grade (p < 0.001). Furthermore, our data revealed higher levels of AR mRNA in BC patients expressing either estrogen or progesterone receptors (p < 0.001). Together, our findings indicate that high mRNA levels of AR are associated with BC subgroups with the less aggressive clinical features.

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Ruyong Formula (RYF) Attenuates the Abnormal Phenotypic Changes of Thymic Epithelial Cells in 4T1 Breast Cancer Mice

10.21203/rs.3.rs-591139/v1 ◽

2021 ◽

Author(s):

Bing-Qian He ◽

Rong-Zhen Shi ◽

Qi-han Luo ◽

Wen-Qin Guo ◽

Xie Xu ◽

...

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Luciferase Reporter ◽

Thymic Epithelial Cells ◽

Mrna Levels ◽

Smad Pathway ◽

Phenotypic Changes ◽

4T1 Breast Cancer ◽

Tgf Β1 ◽

E Cadherin

Abstract BackgroundEpithelialization of the breast epithelial cell is the critical step in breast cancer, but the phenotypic changes of thymus epithelial cells (TEC) and the following immune abnormalities during the development of breast cancer are rarely examined. Ruyong Formula (RYF) has been used for thousands of years, our previous researches have shown it could attenuates atrophied thymic epithelial tissue in breast cancer mice, but the mechanism is still unknown.MethodsHPLC was used to analyze the chemical components of RYF. The 4T1 breast cancer mice model was established to study the anticancer effects of RYF. The efficacy of RYF on tumor volume, anti-tumor rate and organ index were observed. The thymus tissue were stained with Hematoxylin-Eosin (H&E) to observe the morphological changes. Cell phenotype marker, such as E-cadherin, α-tubulin and Vimentin were observed by immunofluorescence staining in TGF-β1-induced iTECs after RYF treatment. The mRNA levels of phenotypic markers and phenotype-related transcription factors, including E-cadherin, Vimentin, Zeb-1, Snail 1 and Smad 2 were detected by qPCR. The effect of RYF on the activation of Smad pathway in TGF-β1 induced iTECs was detected by luciferase reporter assay.ResultsRYF could reduce the metastatic rate and the number of pulmonary metastases in breast cancer mice and increased anti-tumor rates. Compared with the thymus in normal group, RYF increased the number of thymocytes in the cortex regions. In vitro study indicated the EMT promotion effect of TGF-β1, shown as the decreasing of E-cadherin and up-regulation of the Vimentin’s expression. The level of Snail 1 and Zeb 1 increased significantly, and the mRNA levels of Smad 2 was up-regulated. Compared with TGF-β1 group, RYF-treated TECs reversed the proteins expression of E-cadherin and Vimentin and the mRNA levels of Snail 1 and Zeb 1. RYF also promoted the proliferation of iTECs, and confronted the TGF-β1 induced phenotypic transition in iTECs.ConclusionThe abnormal thymic function of breast cancer mice was mainly due to the disorder of cortex and medulla regions cells and the atrophy of cortex. Interestingly, RYF could reverse the phenotypic changes of TECs in breast cancer by inhibiting the TGF-β1/Smad pathway.

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Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana

PLoS ONE ◽

10.1371/journal.pone.0258543 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258543

Author(s):

Francis Opoku ◽

Kweku Bedu-Addo ◽

Nicholas Akinwale Titiloye ◽

Elijah Atta Manu ◽

Charity Ameh-Mensah ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Histological Grade ◽

Phenotypic Expression ◽

Tumour Suppressor ◽

P53 Expression ◽

Protein P53 ◽

Tumour Suppressor Protein ◽

Mdm2 Expression

Background Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort. Method A 9-year retrospective cross-sectional study on archived tissue blocks–formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes. Results The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05). Conclusion The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.

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