Association of p53 codon 72 polymorphisms with expression status of hormone receptors like ER, PR, and HER-2 in invasive ductal breast carcinoma in Bangladeshi women

Objective : This study explores the correlation between the expression of E-cadherin, p53 tumor suppressor gene, c-erb-B2 (HER-2/neu) and steroid receptors (ER, PgR) in invasive ductal breast carcinoma with axillary lymph node metastases. Patients and Methods : We have investigated tumor samples from sixty patients with invasive ductal breast carcinoma. 30 of the patients had axillary lymph node metastases and 30 had no axillary lymph node metastases. Tumor tissues of these patients were evaluated by immunohistochemistry for E-cadherin, p53, c-erb-B2 (HER-2/neu) and steroid receptors (ER, PgR). Results : E-cadherin staining was not expressed in 39 patients (65%) with invasive ductal breast carcinoma. ER, PgR, p53, and c-erb-B2 signals were positive in 36 (60%), 26 (43.3%), 33 (55%), and 29 (48.3%) of the patients, respectively. PgR and c-erb-B2 expression was associated with lymph node metastases (p=0.009, p=0.001, respectively). No association was found between the reduced E-cadherin protein and age. The presence of E-cadherin was associated with axillary lymph node metastases and p53 (p<0.009, p<0.001, respectively). Conclusion : We found that, the p53 protein may play a role in regulation of E-cadherin protein expression in invasive ductal breast carcinomas with axillary lymph node metastases. Keywords : Breast carcinoma, E-cadherin, p53, c-erb-B2, ER, PgR, Metastases

Breast cancer heterogeneity in histology and molecular subtype influences metabolic and proliferative activity and hence the acid load on cancer cells. We hypothesized that acid-base transporters and intracellular pH (pHi) dynamics contribute inter-individual variability in breast cancer aggressiveness and prognosis. We show that Na+,HCO3– cotransport and Na+/H+ exchange dominate cellular net acid extrusion in human breast carcinomas. Na+/H+ exchange elevates pHi preferentially in estrogen receptor-negative breast carcinomas, whereas Na+,HCO3– cotransport raises pHi more in invasive lobular than ductal breast carcinomas and in higher malignancy grade breast cancer. HER2-positive breast carcinomas have elevated protein expression of Na+/H+ exchanger NHE1/SLC9A1 and Na+,HCO3– cotransporter NBCn1/SLC4A7. Increased dependency on Na+,HCO3– cotransport associates with severe breast cancer: enlarged CO2/HCO3–-dependent rises in pHi predict accelerated cell proliferation, whereas enhanced CO2/HCO3–-dependent net acid extrusion, elevated NBCn1 protein expression, and reduced NHE1 protein expression predict lymph node metastasis. Accordingly, we observe reduced survival for patients suffering from luminal A or basal-like/triple-negative breast cancer with high SLC4A7 and/or low SLC9A1 mRNA expression. We conclude that the molecular mechanisms of acid-base regulation depend on clinicopathological characteristics of breast cancer patients. NBCn1 expression and dependency on Na+,HCO3– cotransport for pHi regulation, measured in biopsies of human primary breast carcinomas, independently predict proliferative activity, lymph node metastasis, and patient survival.

Objective To investigate the expressions of progesterone receptor a and b in breast invasive ductal carcinoma(IDC) and their associations with clinical and pathological factors and prognosis. Methods The expressions of PR-a and PR-b in 100 specimens of IDC were detected by immunohistochemistry. The correlations between PR-a, PR-b and characteristics such as ER-α, ER-β, HER-2, Ki-67, axillary lymph node(ALN)metastases, cytological classification, TNM staging and lymphovascular invasion were analyzed, the relationships between PR-a/PR-b ratio and these factors were investigated. Results The expression rates of PR-a and PR-b were 55% and 58% respectively. The results showed positive correlation between PR-a and HER-2, Ki-67(P 1, =1 and 1 group, the positive rates of HER-2, Ki-67, high cytological classification, high TNM staging and ALN metastases were higher than PR-a/PR-b≤1 group(P < 0.05). Conclusions The expression of PR-b is negatively correlated with HER-2, Ki-67, ALN metastases, cytological classification, TNM staging and lymphovascular invasion. PR-b positive and PR-a/PR-b≤1 can be good indicators of prognosis for IDC. Key words: Invasive ductal carcinoma(IDC); Progesterone receptor a(PR-a); Progesterone receptor b(PR-b); Prognosis

We evaluated the relationship between the DNA ploidy status and other variable prognostic factors, especially regional lymph node metastases, in 121 patients with invasive ductal carcinoma of breast, together with the value of these factors in estimating the prognostic of breast cancer. The ploidy status was diploid in 40% of the patients, and aneuploid in 60%. A significantly higher incidence of aneuploidy was found in patients with more than 4 positive axillary lymph nodes, positive internal mammary lymph nodes, or clinical stage 3 of malignancy. In a univariate study, overall survival and disease-free survival were significantly correlated with axillary and internal mammary lymph node metastases, tumor size, and clinical stage of malignancy. The disease-free survival rates for the diploid group tended to be somewhat higher than those for the aneuploid group of patients without axillary lymph node metastases. In the multivariate analysis, however, only axillary lymph node metastasis was significantly correlated with overall survival and disease-free survival. There was also a trend for the internal mammary lymph node metastases to be correlated with survival. As the DNA ploidy status was closely correlated with the axillary and internal mammary lymph node metastases, it did not appear to be an independent prognostic factor in this small series.

Context:Fine needle aspiration cytology (FNAC) plays an important role in the diagnosis of breast carcinoma. However, its role as a prognostic tool needs to be explored. This can be achieved by studying its correlation with an established prognostic marker such as axillary nodal metastasis.Aims:This study was undertaken to correlate the cytological features of invasive ductal carcinoma (IDC) of breast with axillary lymph node status.Settings and Design:Tertiary care hospital, retrospective analytical study.Materials and Methods:The study group included 150 cases of IDC of breast diagnosed on FNAC, who had subsequently undergone modified radical mastectomy. Cytologic grades were assigned as per Robinson's grading system. Histopathological sections of axillary lymph nodes were assessed for metastasis.Statistical Analysis Used:The cytologic grade and each feature of the cytologic grade were correlated with the lymph node metastasis using χ2 test. Values of P < 0.05 were considered significant.Result:A statistically significant correlation was noted between cytologic grade of tumor and axillary lymph node metastasis (P < 0.05). In addition, a positive correlation was found between two of the individual features of cytologic grade, namely, nuclear size and cell uniformity with axillary lymph node metastasis (P < 0.05).Conclusion:Robinson's cytologic grade of breast carcinoma correlates well with the presence of axillary lymph node metastasis and hence can be used as a prognostic tool. As there is an increasing trend toward conservative approach to management of breast carcinoma, patients receive preoperative neoadjuvant therapy which may alter the nodal status on the resected specimen. Hence, a high cytological grade of primary tumor, as assessed on FNAC before initiation of therapy, should alert the treating team of the possibility of axillary lymph nodal metastasis.

To investigate the expression of fatty acid synthase (FAS) in adenosis, atypical ductal epithelial hyperplasia, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of breast, and the correlation of FAS expression with HER2 gene amplification in IDC. Immunohistochemical EnVision method staining for FAS was performed in 100 cases of breast lesions and 10 normal breast tissues. HER2 gene amplification was detected with FISH in 60 cases of IDC. The cohort included 10 cases of adenosis, 10 atypical ductal epithelial hyperplasia, 20 DCIS (8 high-grade, 9 intermediated-grade and 3 low-grade), and 60 cases of IDC (5 grade 1, 40 grade 2 and 15 grade 3). FAS expression was negative in all 10 normal breast tissues; in the 10 cases of adenosis, strongly positive FAS expression was detected in one case, positive in 2, weakly positive in 4, and negative in 3; in the 10 cases of atypical ductal epithelial hyperplasia, FAS immunohistochemistry showed that 1 was strongly positive, 4 positive, 4 weakly positive, and 1 negative; in the 20 cases of DCIS, FAS immunostaining showed that 12 were strongly positive, 5 positive, 1 weakly positive, and 2 negative; FAS expression showed a clear increasing trend from normal breast tissue, atypical ductal epithelial hyperplasia to DCIS (χ(2) = 42.02, P < 0.01). Likewise, the increasing trend was also demonstrated from adenosis to DCIS (χ(2) = 34.69, P < 0.01). There was also a positive correlation between FAS expression and extent of lesion among normal breast tissue, adenosis, atypical ductal epithelial hyperplasia and DCIS (χ(2) = 86.02, P < 0.01; r = 0.568, P < 0.01). FAS expression was not correlated with the grade of DCIS (χ(2) = 9.12, P = 0.16). In the five cases of grade 1 IDC, FAS immunostaining showed that 4 cases were strongly positive and 1 positive; in the 40 cases of grade 2 IDC, FAS immunostaining showed that 27 strongly positive, 12 positive, and 1 negative; in the 15 cases of grade 3 IDC, FAS immunostaining showed that 6 were strongly positive, 5 positive, 3 weakly positive, and 1 negative; FAS expression was stronger and more extensive in DCIS, IDC grades 1 and 2 than that in other groups. However, FAS expression was weaker in the IDC grade 3 (χ(2) = 11.26, P = 0.01). The positive expression rate of FAS in IDC was generally higher than that in benign breast lesions (χ(2) = 47.19, P < 0.01). In the 60 cases of IDC, FISH showed HER2 gene amplification in 22 cases, but not in the remaining 38 cases. FAS expression in IDC was highly correlated with HER2 gene amplification (r = 0.44, P < 0.01). The expression of FAS had significant correlation with status of ER and PR and tumor size (P < 0.05). There was no significant correlation with age, immunohistochemical HER2 expression, lymph node metastasis and clinical stage (P > 0.05). FAS may be closely related to the carcinogenesis of breast IDC. FAS expression is closely associated with HER2 gene amplification in IDC.

Context: The expression of p40 in breast tissue as a myoepithelial marker is not extensively studied. This study was designed to find the expression of two markers p63 and p40 in benign breast diseases and Invasive ductal carcinomas (IDCs) of the breast. Aim: A series of cases of fibroadenoma and IDC of breast were studied for expression of p40 and compared to the p63 staining profile. Settings and Design: A total of 118 cases of breast disease were selected for this study from the archives of a tertiary care hospital, which included 41 cases of benign and 77 cases of malignant etiology. After the exclusion, 30 cases of fibroadenoma and 68 cases of IDC, were selected for the study. Subjects and Methods: Samples (n = 98) included fibroadenoma (n = 30) and IDC (n = 68). IDC was studied as a whole group and was also divided as triple negative breast cancer (TNBCs, n = 12) and Non-Triple TNBCs (NTNBC, n = 56). The expression of p63 and p40 was assessed in myoepithelial cells (MECs) in fibroadenoma and tumor cells in IDC. Results: Both the antibodies performed similarly to highlight MECs in fibroadenoma in all 30 cases. In IDC, TNBC and NTNBC subgroups p63 stained the tumor cells more than p40. None of the tumor cells in the NTNBC group exhibited positivity for p40. Conclusions: As a MEC marker, both p63 and p40 perform similarly but in IDC (TNBC and NTNBC), the tumor cells of IDC stain significantly more for p63 than p40. It appears that p40 does not come positive in the tumor cells of NTNBC.

Background: Human epidermal growth factor receptor 2/neu (HER2/neu) assessment is carried out in gastric adenocarcinomas (GAC) and invasive ductal carcinoma (IDC) breast to decide upon of trastuzumab targeted therapy. The study the only of its kind which has compared the influence of HER2/neu expression to markers of tumor aggression in these two malignancies in similar target population. Material and Methods: HER2/neu evaluation was conducted by immunohistochemistry (IHC) using the guidelines of Trastuzumab for Gastric Cancer trial for GAC and ASCO-CAP 2013 for IDC breast. The study correlated HER2/neu expression with markers of tumor aggression. Aims: The present retrospective study compares the disease influence of HER2/neu over expression on markers of disease aggression like age at presentation, grade of tumor and lymph node metastasis in GAC and IDC. Results: We have compared 82 cases of GAC with 113 cases of IDC. HER2/neu expression was seen in 23.2% and 36.3% of GACs and IDCs respectively. The mean age of HER2/neu positive GACs was found to be 3.47 years greater than their negative counterpart but the pattern was reversed in cases of IDC breast where the mean age of HER2/neu positive tumors was 6.09 years less than their negative counterpart. Though no correlation was found between grade of tumor and HER2neu status in GACs (P = 0.2930), however in IDC breast a significant correlation HER2neu positivity was found with higher grade (P = 0.0002). Similarly though we did not find any correlation of HER2neu status with nodal metastasis in GACs (P 0.0511) but in IDCs a significant correlation was found of nodal metastasis with HER2/neu positivity (P = 0.0001). Conclusion: We conclude that HER2/neu expression is more frequent in IDC breast and is significantly associated with markers of aggression in contrast to its influence on the same markers in GACs.

Objective To study the expression and significance of P33/ING1 and HIF-1α in invasive ductal carcinoma of breast(IDC).Methods Immunohistochemical SP method was performed to detect the expression of P33/ING1 and HIF-1α in 68 cases of IDC and 20 cases of breast fibroadenoma and the relationship between the expression and clinical-pathological characteristics was analyzed.Results The positive expression rates of P33/ING1 protein in IDC was significant lower than that in breast fibroadenoma(60.29% vs.95%;P0.01);and negatively correlated with tumor size,axillary lymph node metastasis and histologic grade(P0.05).The positive expression rates of HIF-1α protein in IDC was significant higher than that in breast fibroadenoma(52.94% vs.10%;P0.01) and positively correlated with axillary lymph node metastasis and histologic grade(P0.05).There was a negatively correlation between P33/ING1 and HIF-1α in IDC(r=-0.283;P0.05).Conclusion There were low-expression of P33/ING1 and over-expression of HIF-1α in IDC.P33/ING1 and HIF-1α proteins were significantly correlated with the clinicopathological characteristics in IDC.Combined detection of P33/ING1 and HIF-1α might calculate the biological behaviors of IDC.

Objective To evaluate the relation of appearance of contrast-enhanced ultrasonography (CEUS) to Ki 67 and C-erbB-2 in breast invasive ductal carcinoma and ductal carcinoma in situ.Methods The appearance of CEUS in 29 patients with breast invasive ductal carcinoma and 12 patients with ductal carcinoma in situ,which was diagnosed by surgery or biopsy,was analysed retrospectively.The Ki-67 and CerbB-2 were measured by immunohistochemical test.The relation of the above two factors to appearance of contrast ultrasonography was analysed.Results The positive rate of Ki-67 was 68.97％ (20/29) in patients with breast invasive ductal carcinoma and 16.67％ (2/12) in patients with ductal carcinoma in situ.The positive rate of C-erbB-2 was 48.2％ (14/29) in patients with breast invasive ductal carcinoma and 42.6％ (5/12) in patients with ductal carcinoma in situ.The masses had a common appearance of high enhance in patients with breast invasive ductal carcinoma and ductal carcinoma in situ,which was not correlated to C-erbB-2.The Ki-67 was significantly higher in patients with ductal carcinoma in situ than that in patients with breast invasive ductal carcinoma,the appearance of CEUS was correlated to Ki 67.Conclusions The features of micro-vessels by CEUS were correlated to Ki-67 in patients with breast invasive ductal carcinoma and ductal carcinoma in situ. Key words: Ultrasonography ; Microbubbles ; Breast neoplasms ; Ki-67 antigen; Genes, C-erbB-2

Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma

Unusual collision tumor with infiltrating ductal carcinoma and breast skin squamous cell carcinoma: A case report and literature review

Objective To explore the expression of Cullin7 protein in breast invasive ductal carcinoma and its relationship with the clinicopathological factors.Methods The expression of Cullin7 protein was detected in 13 cases of normal breast tissues,20 cases of benign breast tumor,68 cases of breast cancer and 32 cases of axillary lymph node metastasis of breast cancer tissue samples by immunohistochemical streptavid-in-peroxidase (SP) method.Results The positive expression rate of Cullin7 in normal breast tissue,benign breast tumor,breast invasive ductal carcinoma and axillary lymph node metastases of breast cancer was 0,30.0％,55.9％,and 78.1％ respectively.The positive expression rate of Cullin7 in the axillary lymph node metastases of breast cancer was significantly higher than the other three kinds of tissue samples (P ＜ 0.05).Cullin7 protein expression had no obvious correlation with the menopausal status,tumor size,clinical stage or pathological type P ＞ 0.05),but had a significant correlation with tissue differentiation degree and axillary lymph node metastasis (P ＜ 0.05).Cullin7 protein expression in breast cancer tissue was significantly negatively correlated with estrogen receptor (ER,P ＜ 0.05),but not with progesterone receptor (PR),and human epidermalgrowth factor receptor-2 (Her-2,P ＞ 0.05).Conclusion Cullin7 may play an important role in the development,invasion and metastasis of breast cancer. Key words: Breast carcinoma ; Transfer; Cullin7

The overexpression of heat shock protein 27 (hsp-27) in early-stage breast cancer is associated with histopathologic features of poor prognosis and clinically with an increased probability of disease recurrence. Hsp-27 is overexpressed in 25% of invasive ductal carcinomas (IDC); however, its distribution in ductal carcinoma in situ (DCIS) and DCIS associated with IDC has not been investigated. We postulated that hsp-27 might be detected and variably expressed in DCIS and, like HER-2/neu oncoprotein expression, might be a tumor-specific marker worthy of future clinical investigation. To test these hypotheses, the distribution of hsp-27 in noncomedo and comedo DCIS, and DCIS associated with IDC, was evaluated by immunohistochemistry and compared with HER-2/neu expression within the same cancers. Hsp-27 was overexpressed in 28 of 47 (approximately 60%) cases of DCIS; expression in pure DCIS was 16 of 24 (67%), and 12 of 23 (approximately 50%) in DCIS associated with IDC. Hsp-27 expression by in situ and invasive components of the same neoplasm were concordant in 22 of 23 (approximately 95%) cases tested. Comedo variants appeared to have somewhat higher hsp-27 expression than noncomedo DCIS, whether or not there was an associated IDC. These results are reminiscent of HER-2/neu oncoprotein expression in DCIS and DCIS associated with IDC observed by others. However, although 4 of 22 (18%) cancers containing DCIS + IDC expressed HER-2/neu, no relationship with hsp-27 expression in the same cancers was observed. We found a high incidence of hsp-27 overexpression in DCIS and in DCIS associated with IDC. This rate is twice that previously observed in IDC alone. Hsp-27 expression is independent of HER-2/neu expression.

Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.