c-erbB2 Expression Research Articles

Correlation with MRI features, cell density and the expression of immunohistochemistry of pure mucinous breast carcinoma

Objective: To explore the MRI features of the pure mucinous breast carcinoma(PMBC) and the correlation with cell density and the expression of immunohistochemistry. Methods: MRI features of 35 pure mucinous carcinomas were retrospectively analyzed from January 2011 to May 2016 in Guangdong General Hospital. MR images were reviewed for shape, margin, the signal intensity, enhancement patterns of tumors and diffusion weighted imaging (DWI) features and apparent diffusion coefficient (ADC) value. All the patients were detected by immunohistochemical staining with expression of ER, PR, CerbB-2, Ki-67 and Her-2. Correlations between MRI features of PMBC and cell density and the expression of immunohistochemistry were analyzed. Results: A total of 16 oval masses(16/35, 45.7%) and 10 round masses(10/35, 28.6%)were found in 35 PMBC with clear boundary(26/35, 74.3%) and lobulated shape(31/35, 88.6%). Very high signal intensity on T(2)-weighted images was found in 33 PMBC (33/35, 94.3%) and early enhancement rate was 115%±9% for PMBC. 28 PMBC demonstrated persistent enhancing pattern on time-signal intensity curve and 7 PMBC demonstrated plateau pattern.Mean ADC value was (1.91±0.06)×10(-3)mm(2)/s for PMBC. There was significant difference with early enhancement rate and ADC value between PMBC with more or less quantities of cellular mucin (P<0.05). There was no significant difference with ER, PR, CerbB-2, Her-2 and Ki-67 expression between PMBC with more or less quantities of cellular mucin (all P>0.05). Conclusions: PMBC has distinctive MRI features. The prognosis of PMBC is better from correlation between MRI features, cell density and the expression of immunohistochemistry.

GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas

GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.

Expressions of Estrogen Receptor,Progestogen Receptor,Cerb-B2,and Ki67 Index in the Simple Mucinous Carcinoma of the Breast

To approach the expressions of estrogen receptor (ER),progestogen receptor (PR),Cerb-B2,and Ki67 index in simple mucinous carcinoma of the breast and their clinical significance. The clinicopathological data of 72 patients with simple mucinous carcinoma of the breast who were treated in our hospital from 1997 to 2012 were retrospectively studied. Expressions of ER,PR,Cerb-B2,and Ki67 index and their relationship with clinical characteristics were analyzed. Nine patients had lymph node metastasis. Expressions of ER,PR,and Cerb-B2 were 77.8%,69.4%,and 3.1%,respectively. The expressions of ER,PR,and Cerb-B2 showed no correlation with age,menstrual status,and axillary lymph node metastasis (P>0.05). The expression of ER was correlated with tumor diameter (P=0.008) while the expression of PR and Cerb-B2 showed no such correlation. High ER or PR expression and low Cerb-B2 expression predict good prognosis in patients with simple mucinous carcinoma of the breast. Combined detection of ER,PR,Cerb-B2,and Ki67 index may help to improve the multidisciplinary management of simple mucinous carcinoma of the breast.

Expression of ER, PR, C-erbB-2 and Ki-67 in Endometrial Carcinoma and their Relationships with the Clinicopathological Features.

To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

Cadmium exposure and the risk of breast cancer in Chaoshan population of southeast China.

Recently, there is increasing evidence indicating a link between cadmium exposure and human breast cancer. This study was aimed to explore the relationship between blood cadmium burden and the risk of breast cancer in Chaoshan women with no occupational exposure. Blood cadmium levels (BCLs) were determined in whole blood of 186 breast cancer cases and 139 controls. Basic clinical data and information of age, occupation, blood types, family cancer history, and disease history, as well as other demographic characteristics were collected from medical records. BCLs were detected by graphite-furnace atomizer absorption spectrophotometer (GFAAS). BCLs and proportions of BCLs over 3 μg/L between cases and controls were compared. The relationships between BCLs and breast cancer were explored by comparing BCL differences between/among different characteristics of investigated factors. In addition, BCLs within cases were also compared in relation to the disease clinical stages, tumor-node-metastasis (TNM) stages, and estrogen receptor (ER), progesterone receptor (PR), and Cerb-B2 expressions. The breast cancer patients had a higher median concentration of blood cadmium (2.28, interquartile range 1.57-3.15 μg/L) than the controls (1.77, 1.34-2.57 μg/L; P = 0.001). The proportion of BCLs over 3 μg/L was 2.35 times higher in the breast cancer cases than that of the controls after adjusting for age. Cadmium tends to accumulate in the human body with age and body mass index (BMI) but not associates with type of job, family history, disease history, and other investigated characters. With the increase of clinical stages and T and M stages, the BCLs in the breast cancer cases also increased. BCLs were positively associated with Cerb-B2 expression (r = 0.152, P = 0.038) but not significantly associated with ER and PR expressions. The data obtained show that cadmium concentration is significantly higher in blood of breast cancer patients in comparison to healthy controls. Cadmium seems to be a risk factor of breast cancer, and high cadmium exposure was observed in advanced stages of this disease, which indicates that it may promote the development of breast cancer.

Question about Liu Y et al. entitled "Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from eight studies".

We read with great interest on the recent paper by Liu Y et al. "Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from eight studies" published online in Tumor Biology (Tumor Biol 5(9):8939-43, 2014). The investigators (Liu Y et al.) performed a meta-analysis to study the relationship between c-erbB2 expression and prognostic impact in patients with osteosarcoma. They conducted a comprehensive and detailed meta-analysis to reveal the prognostic role of c-erbB2 for osteosarcoma. As a result, eight studies with 411 osteosarcoma patients were involved to estimate the relationship. Positive expressions of c-erbB2 predicted poorer survival in osteosarcoma patients with the pooled RR of 1.53 (95 % CI 1.20-1.94, P = 0.0006). Finally, they concluded that c-erbB2 overexpression is related to poor prognostic of osteosarcoma and can be a useful clinical prognostic factor for those patients. Nevertheless, we have several queries which we would like to communicate with them.

Abstract P6-02-06: Safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide

Abstract Background The introduction of neoadjuvant chemotherapy considerably changed the natural history of breast cancer by permitting a big tumors to be operable, permitting less aggressive surgical procedures and when achieving complete pathological response prolonging the disease-free period. However, the chemotherapy schemes bear high toxicity rates and are even life-threatening. Neoadjuvant chemotherapy aims at reducing mortality and improving surgical options and offers an in vivo chemosensitivity testing at the same time. It is the ideal setting for clinical and translational research. Compared to the classical adjuvant treatment, it offers several advantages. Methods We performed a pilot study to evaluate the safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide in comparison to the classical neoadjuvant chemotherapy paclitaxel, adriamicyn and cyclofosfamide (TAC). All the patients were women with recently diagnosed breast cancer who needed primary chemotherapy as the first treatment selected from Perola Byington Hospital in São Paulo - Brazil. Results From April 2006 to June 2008, 39 patients from a center for breast disorders (Pérola Byington Hospital) were included in the study. These patients were randomized to the standard chemotherapy scheme (control arm – n=16) or LDE-paclitaxel (LDE arm – N=17). Six patients were excluded from the study because they did not complete at least 5 cycles of chemotherapy. We also excluded three patients because of lack of follow up. The majority of patients had stage III (37% IIIA and 27% IIIB). There was no significant difference among the groups, considering the clinical variables, so the sample was considered homogeneous. The patients were grouped in four different groups regarding the expression of ER, PR and CerbB2: Luminal subtype, Triple Negative, Her2-positive and Hybrid Luminal. We observed 37,5% of complete response in the control arm and 23,5% in the LDE arm. The partial response were 43,7% in the control group and 58,8% in the LDE group. The toxicity particularly in grade 3 and 4 events were substantially lower in LDE group: Nausea 11% vs 2,2%; Vomiting 7,3% vs 0.7% and neutropenia 8,8% vs 2,2%. Conclusion LDE scheme was effective and had lower grad 3 and 4 events than the TAC regiment. More studies are necessary to evaluate this approach. Citation Format: Andre Mattar, Luciana B Ferreira, Luiz H Gebrim, Roberto Hegg, Raul C Maranhão. Safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-06.

Expression of DDR1 and DVL1 in invasive ductal and lobular breast carcinoma does not correlate with histological type, grade and hormone receptor status.

Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

Cytological Evaluation of Tongue Cells and Buccal Mucosa Cells

Objective: C-erbB-2 expression has been detected in 40 to 60% of head and neck squamous cell carcinomas (HNSCC). With regard to preneoplastic lesions, thus suggesting that the loss of CerbB-2 expression is a carcinogenic molecular event. Study Design: This study was conducted on a total of 20 paraffin-embedded HNSCC samples, which were histopathologically diagnosed at the Department of Pathology of medicine Hospital between 2010 and 2011. Paraffin-embedded HNSCC samples 3 mm in thickness, were then cut. The slides were stained with C-erbB-2. Results: There was significant relationship between staining density and differentiation grade (R1⁄4 0,922671). Conclusions: Consequently, it was concluded that cerbB-2 is a poor prognostic factor in HNSCC like in breast tumour.

P53 expression in breast cancer predicts tumors with low probability of non-sentinel nodes infiltration.

Several predictive tools of non-sentinel lymph nodes neoplastic involvement when a positive sentinel lymph node is found have been described. However, molecular factors have been rarely evaluated to build these tools. The aim of this study was to establish which factors predicted non-sentinel lymph nodes infiltration in our setting, including some molecular factors. We carried out a retrospective review of 161 patients with breast cancer and a positive sentinel lymph node who had undergone axillary lymph node dissection, none of whom had received neoadjuvant treatment. Features evaluated as predictive factors for non-sentinel node positivity were: menopausal status, tumor size, histological subtype, histological grade, lymphovascular invasion, extracapsular invasion, Ki67 index, hormonal receptors, CerbB2 and p53 expression, size of sentinel lymph node metastases and number of sentinel lymph nodes affected. Tumor size (P = 0.001), size of sentinel lymph node metastases (P = 0.001), lobular invasive carcinoma (P = 0.05) and lymphovascular invasion (P = 0.006) were significantly associated with non-sentinel lymph node positivity. Tumor p53 positive expression was strongly associated with non-sentinel lymph node negativity (P = 0.000). In multivariate analysis, all these factors but tumor size maintained their significance. The discrimination power of the model calculated by the area under the receiver-operator curve was 0.811 (95% confidence interval, 0.741-0.880). p53 expression in breast cancer was highly predictive of non-sentinel lymph node negativity in our study. New studies should evaluate if it would be useful to add p53 expression to other existing predictive tools.

Hormone receptor, HER2/NEU and EGFR expression in ovarian carcinoma--is here a prognostic phenotype?

We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

Relationship between FAT10 expression and biological behaviors in infitrating ductal carcinoma of breast

To study the relationship between FAT10 expression and biological behaviors in infitrating ductal carcinoma of breast. The expressions of diubiquitin (FAT10), estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 in 50 cases of infitrating ductal carcinoma of breast were detected by immunohistochemistry. Western blot was used to detect FAT10 expression in MB-MDA-435, MB- MDA-435-transfected with FAT10 siRNA expression plasmid, MCF-7 and MCF-7-transfected with FAT10 expression plasmid, respectively. Transwell was used to detect invasion capability of MB- MDA-435, MB-MDA-435-transfected with FAT10 siRNA expression plasmid, MCF-7 and MCF-7-transfected with FAT10 expression plasmid. The expression intensity of FAT10 was significantly correlated to patho-grading, lymph nodes metastasis, distant metastasis and TNM staging (P<0.01), but not to age of patients and tumor sizes in infitrating ductal carcinoma of breast (P>0.05). The expression intensity of FAT10 in receptor- negative group was obviously stronger than that in receptor- positive group (P<0.01). The expression intensity of FAT10 in triple-negative breast cancer was significantly stronger than that in non- triple-negative breast cancer (P<0.01). The survival rate of patients with FAT10 positive expression was significantly lower than negative ones (P<0.05). Western blot results showed that FAT10 intensity in MB-MDA-435 significantly higher than that in MCF-7. Up-regulation expression of FAT10 could obviously increase the invasion capability of MCF-7, and downregulation of FAT10 could significantly decrease the invasion capability of MB-MDA-435 (P<0.01). FAT10 might increase the invasion capability of breast cancer cells by direct or indirect ways, and play an important role in invasion and metastasis of breast cancer. FAT10 might be an independent index for evaluation of breast cancer prognosis, and a potential target for breast cancer therapy, especially for triple-negative breast cancer.

The effect of tamoxifen on expression of ER, PR, Cerb-B2, and ki-67 in C3H mice spontaneous breast cancer model and the relation with chemotherapeutic effect.

To explore the effect of tamoxifen on expression of ER, PR, Cerb-B2, and ki-67 in C3H mice spontaneous breast cancer model and further explore its relation with chemotherapeutic effect. Forty male C3H mice with spontaneous breast cancer aged 10 months were selected, and randomly divided into model group and tamoxifen group, with 20 mice in either group. Model group received intraperitoneal injection of normal saline, tamoxifen group received 5 mg/Kg tamoxifen injection. Tumor volume was measured every 3 days for 12 days in total. After that the mice were killed to weigh the tumor for tumor growth inhibition rate calculation; breast cancer specimen was collected, and immunohistochemistry was used to detect ER, PR, Cerb-B2, and ki-67 positive cells, western blot was used to detect expression of ER, PR, Cerb-B2, and ki-67 in breast cancer. The tumor growth inhibition rate of tamoxifen on mice was 61.56 %. Compared with model group, tumor weight in mice from tamoxifen group was significantly lower, tumor growth rate in tamoxifen group was significantly lower than model group; immunohistochemical staining results showed that compared with model group, ER, PR, Cerb-B2, and ki-67 positive cells in tumor of tamoxifen group were significantly lower (P < 0.05). Among them, ki-67 expression in tamoxifen group was negative; western blot semi-quantitative results were in accordance with immunohistochemistry results. Tamoxifen is effective on C3H mice spontaneous breast cancer. After being treated with tamoxifen, expression levels of ER, PR, Cerb-B2 and ki-67 are changed, and change of ER, PR, Cerb-B2, and ki-67 can predict the therapeutical effect of tamoxifen.

The diplotype Fas -1377A/-670G as a genetic marker to predict a lower risk of breast cancer in Chinese women.

This study was designed to reveal the effects of Fas and FasL polymorphisms of interest on breast cancer risk. A total of 439 patients with breast cancer and 439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas -670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of estrogen receptor, progesterone receptor, and CerbB-2 were determined by immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of breast cancer and adjacent normal tissues were detected by real-time polymerase chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA, Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was associated with the opposite effect. Furthermore, gene-gene interaction analysis revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and -670AA genotypes were associated with higher soluble Fas concentrations than other genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer risk and that Fas polymorphisms are likely to affect breast cancer risk by regulating the soluble Fas concentration.

Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from eight studies.

C-erbB2 (HER-2/neu) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. Numerous studies examining the relationship between c-erbB2 expression and prognostic impact in patients with osteosarcoma have yielded inconclusive results. We therefore conducted a meta-analysis to provide a comprehensive evaluation of the prognostic role of c-erbB2 expression on 5-year survival, which compared the positive and negative expression of c-erbB2 in patients of the available studies. A detailed search was made in PubMed for relevant original articles published in English. Finally, a total of eight studies with 411 osteosarcoma patients were involved to estimate the relationship between c-erbB2 expression and 5-year overall survival. Positive expressions of c-erbB2 predicted poorer survival in osteosarcoma with the pooled RR of 1.53 (95 % CI 1.20-1.94, P = 0.0006). In conclusion, the findings from this present meta-analysis suggest that c-erbB2 overexpression is related to poor prognostic of osteosarcoma and can be a useful clinical prognostic factor for those patients.

Immunohistochemical expression of P16 and HER2/neu in normal oral mucosa, oral epithelial dysplasia, and oral squamous cell carcinoma

Background: Oncogenesis in the oral cavity is widely believed to result from cumulative genetic alterations that cause a transformation of the mucosa from normal to dysplastic to invasive carcinoma. The p16 gene produces p16 protein, which in turn inhibits phosphorylation of retinoblastoma (Rb), p16 play a significant role in early carcinogenesis. A number of epidermal growth factor receptor (EGFR) family, HER2/neu, has received much attention because of its therapeutic implications. The aims of the study were to evaluate and compare the immunohistochemical expression of the cell cycle protein P16 INK4a and c-erbB2 (HER2/neu) in NOM, OED, and OSCC. Correlate both marker expression with each other as well as with various clinicopathological findings. Materials and methods: Sixty two formalin-fixed, paraffin embedded tissue blocks (20 cases of normal oral mucosa, 17 cases of oral epithelial dysplasia, and 25 cases of oral squamous cell carcinoma) were included in this study, an immunohistochemical staining was performed using anti p16 monoclonal antibody, and anti HER2/neu polyclonal antibody. Results: Positive IHC expression of p16 was found in 18 cases (90%) of NOM, 16 cases (94.1%) of OED and in 20 cases (80%) of OSCC. Positive IHC expression of HER2/neu was almost undetectable in NOM, while it was found in 9 cases (52.9%) of OED, and in 15 cases (60%) of OSCC.The correlation between the expression of both markers were statistically highly significant in NOM, significant in OED, and non significant in OSCC. Conclusions: This study signify the important role of p16 and HER2/neu in oral carcinogenesis and in the evolution of the mucosa from normal to dysplastic to invasive carcinoma

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p=0.05), prolonging the RF survival of the patients (p=0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily that is involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. We immunohistochemically examined the expression of androgen receptor, basal markers (CK14, 34βE12) and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin–biotin method, and correlated the findings with clinical outcome. Positive androgen receptor expression was defined as staining of 1% or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan–Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38% of tumors, with the proportion of stained tumor cells ranging from 1 to 95% (mean 29%, median 10%). Androgen receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34βE12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with androgen receptor expression. Disease-free survival was significantly better in androgen receptor-positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in both triple-negative and basal-like tumors (hazard ratio, 0.704; 95% confidence intervals, 0.498–0.994; P=0.0464; and hazard ratio, 0.675; 95% confidence intervals, 0.468–0.974; P=0.0355, respectively) was noted within 5 years of diagnosis but not thereafter. Our study suggests that loss of androgen receptor in triple-negative breast cancers augurs a worse prognosis, including those with basal-like features. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor-expressing triple-negative tumors, needs to be performed.

Estrogen Receptor-Negative Breast Ductal Carcinoma: Clinicopathological Features and Mib-1 (Ki-67) Proliferative Index Association

Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.

The expression of EGFR, cerbB2, p16, and p53 and their relationship with conventional parameters in squamous cell carcinoma of the larynx*

To investigate the expression of epidermal growth factor receptor-HER1 (EGFR), cerbB2 (HER2), p16, and p53, as well as the relationship of the expression of these genes with conventional parameters in squamous cell carcinoma (SCC) of the larynx. Samples from 92 cases of diagnosed laryngeal SCC between 2001 and 2011 from the Pathology Department of Ministry of Health Ankara D1şkapi Yildirinm Beyazit Teaching & Research Hospital were studied by immunohistochemistry using EGFR, cerbB2, p16, and p53 antibodies. An increase in the TNM stage and pathological tumor size status correlated with an increase in EGFR and cerbB2 expression. In the cases with lymphovascular invasion, the expression was detected at a higher ratio. Cases in which high levels ofpl6 and p53 expression were observed did not show any lymphovascular invasions. Expressions of p53 and p16 were considered to be most effective in early carcinogenesis stages of laryngeal SCC. In comparison with p53 and p16 expression levels, EGFR and cerbB2 expression levels were observed to be associated with poor prognostic parameters and were higher at later stages of laryngeal carcinogenesis development.