Neu Expression Research Articles

Correlation of HER2/neu receptors and other prognostic factors in breast carcinoma

Background: Breast cancer is the most common malignancy and the leading cause of cancer related death among women all around the world. Evaluation of prognostic factors including biomarkers is highly recommended for the best management and therapeutic decision of breast cancer patients. Aim was to study the correlation of HER2/Neu receptors and other prognostic factors in breast carcinoma.Methods: Patients who are clinically diagnosed as carcinoma breast a detailed history will be taken. Patients were assigned TNM staging according to AJCC classification and posted for surgery than to find out the receptor status from that specimen.Results: In 60 cases, there is no significant correlation and association between the prognostic factors (age, menstrual status, tumour size, side of disease, nodal positivity, pathological subtypes, histological grading except ER receptor positivity PR receptor positivity) and HER2neu receptor positivity. Significant association noted between the HER2NEU receptor positivity and ER, PR receptor negativity. ER AND PR receptor status it shows that a significant proportion of PR receptor activation is independent on ER receptor activation. And also this independent PR receptor positive status give false positive results depends upon staining pattern ,transport method of tissue specimen.Conclusions: Our study results indicate the importance of ER, PR and HER-2/neu expression as prognostic factors for therapeutic decision.

Prognostic Value of HER-2/neu Gene Amplification in Epithelial Ovarian Carcinoma.

Human epidermal growth factor receptor 2 (HER2) has tyrosine kinase activity and is a member of the epidermal growth factor receptor family. This initiates a variety of signal for pathways which leads to cell proliferation and tumourigenesis. In approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers, amplification or overexpression of HER2 occurs, and it serves as a prognostic and predictive biomarker. HER-2/neu is one of the most frequently studied molecular biological parameters in epithelial ovarian cancer (EOC), but its prognostic impact has not been fully assessed. The objective of the current study was firstly to analyse the presence of HER-2 overexpression in EOC patients and secondly to evaluate association between human epidermal growth factor receptor 2 (HER-2/neu) expression and progression-free survival in patients with EOC. In this prospective study of 2years in our department, 186 gynaecological cancers were operated out of which 98 cases were operated for epithelial ovarian cancer and rest for cervical cancer, endometrial cancer, and other subtypes of ovarian cancer. In this study, HER2 gene status was evaluated in EOC by immunohistochemistry analysis, and overall survival of these patients was evaluated. HER-2 overexpression was found in 22 of the 98 investigated cases (22.45%), in which 14 OC (14.29%) were weakly positive and 8 OC (8.16%) were moderately to intensely positive. In the study, increased HER2 expression was associated with decreased progression-free survival (PFS) and hence poor prognosis (P 0.054). The introduction of HER2-directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers. The present study findings provided that HER-2/neu expression in patients with OC has an adverse impact on the PFS. Therefore, our results show that the decision algorithm usually used in breast cancer by HER2 may be appropriate in ovarian cancer.

Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations, while the viral-chemical etiology along with molecular mechanisms of HCC pathogenesis remains largely unknown. This study aimed to determine expression profile and prognostic value of HER-2/neu, STAT3 and SOCS3 in HCC. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the expression of HER-2/neu, STAT3 and SOCS3 in HCC tissues and adjacent normal tissues collected from 176 HCC patients. HER-2/neu and STAT3 levels were higher and SOCS3 expression was lower in HCC tissues than in adjacent normal tissues. HER-2/neu, STAT3 and SOCS3 levels were associated with histological grade, tumor diameter, TNM stage, vascular invasion, lymph node metastasis and distant metastasis in HCC. SOCS3 expression was negatively associated with HER-2/neu and STAT3 expression. HCC patients with higher HER-2/neu and STAT3 levels had shorter overall, disease-free and disease-specific survival, whereas the opposite was found in patients with higher SOCS3 expression. In Cox regression analysis, tumor size, TNM stage, and STAT3 expression were identified as independent prognostic factors of HCC. Taken together, these observations suggest that HER-2/neu, STAT3 and, SOCS3 are related to the aggressive tumor behavior and STAT3 has potential value as a prognostic factor for HCC.

Creating Models to Identify New Therapeutic Options for Aggressive African Breast Cancers

Background: Population-based incidence rates of breast cancer (BC) that does not express the estrogen receptor (ER), progesterone receptor (PR) or overexpress the human epidermal growth factor 2 HER2/ neu (triple negative breast cancer, TNBC) are higher among Africans compared with white women. However the underlying biologic and genetic differences among different ethnicities are poorly understood and there are currently very few ethnically diverse BC models available for identifying new therapeutic options. Aim: Establish an international collaboration to: i, characterize African breast tumors ii, create models for studying these tumors and iii, identify biomarkers for early detection and treatment personalization. Methods: We have collected tumors from 154 white Americans WA, 76 African Americans, AA, 190 Ethiopians, Eth, and 286 Ghanaian (Gh) BC patients. We then established a unique resource of patient derived xenografts (PDX) from these tumors. The PDXs were then fully characterized using whole exome and RNA sequencing for the primary tumor, matched normal DNA, and corresponding low passage PDXs. Using immunohistochemistry, we evaluated the ER, PR, HER2/ neu, androgen receptor (AR), and ALDH1 (cancer stem cell marker) expression among these tumors. Based on biomarker expression the PDXs were then tested against a panel of IND drugs, either alone or in combinations, in an ex vivo organoid culture system to discover potential new therapeutic options. Results: Mean age at BC diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. The proportion of TNBC was significantly higher for the AA and Gh patients (41% and 54%, respectively) compared with the WA and Eth patients (23% and 15%, respectively); P < 0.001. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively ( P = 0.008). The Gh breast tumors exhibited the highest number of loss of function and missense mutations that are likely to impact therapy with a high frequency of P53, APC, and FGFR mutations. These mutations were maintained in the corresponding PDXs that were developed, and were thus used as biomarkers for drug screening. These tumors exhibited a gene expression signature based on the ethnicity of the patients with 2385 genes differentially expressed between Gh and AA, 1573 between AA and CA and 1317 between GH and CA. Results from our ongoing drug screening and biomarker identification will be available soon. Conclusions: Establishing the molecular and genetic platform of aggressive breast cancers occurring in women with African ancestry will help in identifying biomarkers for early cancer detection and targeted treatment stratification for optimum patient outcome. The availability of tumor models based on tumors from diverse African populations is the important missing pieces that have to be incorporated into current drug discovery efforts.

ER, PR and Her-2/neu expression in carcinoma gallbladder

ER, PR and Her-2/neu expression in carcinoma gallbladder

Immunohistochemical her-2/ Neu expression with gene amplification by fluorescence in situ hybridization for assessment in breast carcinomas.

To compare gene amplification of HER-2/neu gene by fluorescence in situ hybridization (FISH) in moderate to strong immunohistochemically (IHS) positive HER-2/neu cases of invasive breast carcinomas. Cross- sectional study. Section of Histopathology, The Aga Khan University Hospital, Karachi, from January 2004 to December 2006. Forty one (41) diagnosed cases of invasive breast carcinomas were included in this study in which already determined immunohistochemical HER-2/neu expression was scored as either 2+ or 3+, based on the intensity of membranous staining. These cases were further evaluated for gene amplification by FISH. For gene amplification, a ratio of HER-2/CEP Z 2 was accepted as positive gene amplification. Out of a total 41 cases, which were scored as 2+ and 3+ by IHC, 14 cases (34.1%; 95% confidence interval: 19%-49.3% ) showed gene amplification by FISH. Proportion of FISH positivity in IHC 2+ cases alone was found to be 25% (95% confidence interval: 10.5%-41%). In contrast, a majority of IHC 3+ cases (5 of 6) were positive by FISH studies. IHC is appropriate for initial HER-2/neu assessment and patients with tumors scored as 3+ may be treated alone based on this information provided strict quality control and 95% concordance with FISH assays; however, patients with tumors interpreted as 2+, would benefit from gene amplification by FISH studies for more accurate assessment to avoid inaccurate prognostication and treatment.

Clinicopathological Evaluation of Abnormal Uterine Bleeding with Special Reference to Estrogen Receptor (ER), Progesterone Receptor (PR)2 and HER-2 / NEU Status

Background: Abnormal Uterine Bleeding (AUB) may be defined as any variation from normal menstrual cycle including alteration in its regularity, frequency, duration of flow and amount of blood loss. AUB can present as menorrhoea, metrorrhagia, poly menorrhoea and dysfunctional uterine bleeding. The study aimed to found out the various aetiopathological factors responsible for AUB. To correlate clinical presentation with histopathological examination and also to study the hormone receptor markers ER (Estrogen Receptors), PR (Progesterone receptor) and marker of oncogene HER-2/NEU for prognostication. Methods: This study was conducted during the period Sept. 2012 to January 2015 in the Department of Obstetrics and Gynecology in collaboration with Dept. of Pathology, Hi-Tech Medical College, Bhubaneswar. 140 patients of 15-55 yrs of age groups were randomly selected excluding pregnant patients and patients below 15 yrs and above 55 yrs. All patients were subjected to Transvaginal-ultransonography, saline infusion sonography and dilation and curettage (D&C) along with endometrial biopsy. All histopathological samples were stained with Hematoxylin and Eosin stain (H&E stain) and subsequently immunostaining was done for ER, PR and HER-2 / NEU. Result: 37.20% cases of AUB were observed in the age group of 41-45. 0.7% among age group of 51-55 yrs. 64.3% of rural population & 67.2% of patients from lower socio-economic group had AUB. 48.6% cases presented with menorrhagia and 42.9% cases had etiological features of dysfunctional uterine bleeding (DUB), 20% had endometrial polyp and 14 cases out of 140 had endometrial carcinoma. In the present study ER were positive in 84.7% and PR were positive in 76.7%. HER-2/NEU expression in this study showed different histopathological pattern of endometrium in AUB. The present study also showed HER-2/NEU expression in 21.4% cases of different grades of Endometrial Carcinoma and all DUB cases showed negative HER-2 / NEU expression. Conclusion: In this study clinical presentation, use of different diagnostic modalities and histopathological correlation were reviewed. Large number of patients belonged to age group 41-50 yrs. The incidence of AUB was maximum in rural areas and most patients belong to lower socio-economic group. By use of Hormone receptors expression of ER & PR and observing the over expression of HER-2 / NEU the prognosis of endometrial lesions can be assessed for early and proper management.

Her-2 Neu Expression in Endometrial Carcinoma

Her-2 Neu Expression in Endometrial Carcinoma

Evaluation of Her-2/NEU Expression in Cell Block Preparation in Breast Carcinoma In Bangladeshi Woman

Background: HER-2 overexpression is associated with clinical outcomes in patient with breast carcinoma. Particularly this is important for target therapies with the monoclonal antibody (Trastuzumab). With aspirated materials from breast carcinoma more information may be retrieved by making cell blocks like immunohistochemistry in the inoperable breast cancer patient. Materials and methods: This study was carried out on 102 female patients with palpable breast lump, among them 33 malignant cases were found and cell blocks were made from the aspirated materials. HER- 2 statuses were estimated in both the cell block preparation and histopathological blocks separately. Results: Among the 33 cases of duct cell carcinoma, cell blocks of 32 cases were found to be adequate but one of them died before the surgery. HER-2 expression score of 0, 1+, 2+ and 3+ were foundin 14, 7, 5 and 5 cases respectively. All the 14 cell block scored as ‘0’ also showed similar ‘0’ score in their corresponding histologic block. Among the seven cell blocks scored as ‘1+’, 5 cases showed ‘1+’ staining and 2 case showed ‘2+’ staining in their corresponding histologic blocks. Of the ‘2+’ cases in cell block, 2 cases failed to correspond as they scored ‘1+’. Finally 5 cell blocks with ‘3+’ scorecorresponded with that of the histologic blocks.In cell block immunohistochemistry, the sensitivity was 71.43%, specificity 91.67%,positive predictive value of 71.43% and a negative predictive value of 91.67% with an accuracy rate of 87.71% with a highly significant p value (<.001). Cohen’s Kappa test of agreement was 0.814 which means there was a good agreement and Spearman’s rank-correlation analysis found to 0.984 with a p value of < .001 which was highly significant. Conclusion: This study found overexpression of HER-2 can be determined with confidence in the cell block preparation, particularly in the negative cases.
 JCMCTA 2017 ; 28 (2) : 88-93

AKT signaling pathway in invasive ductal carcinoma of the breast: correlation with Erα, ERβ and HER-2 expression

Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ERβ expression is a useful biomarker for breast cancer in a manner that is independent of ERa expression. However, studies evaluating ERβ expression with certain tumor variables, such as tumor grade and disease-free survival, had produced conflicting results. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. The current study attempted to compare the relative associations of variables including ERa, ERβ, HER-2/neu and AKT staining with the presence of metastases or survival. Immunohistochemical staining was employed to determine the expression of ERa, ERβ, pAkt and HER-2/neu in 110 cases of primary breast carcinoma. Positive ERa, ERβ, pAkt and HER-2/neu expressions were respectively observed in 46.4% (51/110), 59.1% (65/110), 40.9% (45/110) and 31.8% (35/110) of the tumors. pAkt was significantly associated with HER-2/neu overexpression (P <0.005) and axillary lymph node metastasis (P <0.05). However, there was no significant relationship between pAkt and ERa, ERβ, p53 (P >0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients. The current study suggested that activity of the Akt signaling pathway may indicate a poor prognosis in patients with breast carcinoma. The results implied that estrogen can activate the PI3K-Akt pathway through ERa and ERβ-independent mechanisms in breast cancer.

Role of HER-2/Neu Expression in Premalignant and Malignant Lesions of Uterine Cervix

Role of HER-2/Neu Expression in Premalignant and Malignant Lesions of Uterine Cervix

Gastric adenocarcinoma expressing human epidermal growth factor receptor in South Asian population.

Background/Aim:Gastric cancer is the third leading cause of cancer mortality worldwide. Human epidermal growth factor (Her-2/neu) has shown strong therapeutic implication in breast cancer. Although the prevalence of Her-2/neu over-expression in gastric cancer has been reported across the world, it is still unknown from South Asia. The aim of this study is to evaluate Her-2/neu expression in gastric adenocarcinomas and to correlate with various clinicopathological variables.Patients and Methods:A total of 95 consecutive patients undergoing endoscopic biopsy or gastrectomy were recruited in this study. Clinicopathological parameters of all patients were recorded and hematoxylin and eosin (H and E) staining was performed. Over-expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. To quantify Her-2/neu over-expression, the Hofmann validation scoring system was used and further its association was seen with age, gender, histopathological type, grade, and stage of the tumor. Data were entered and analyzed using SPSS version 21. A P value of <0.05 was considered as significant.Results:Overall, 21 (22.1%) cases were positive for Her-2/neu overexpression from the total of 95 gastric adenocarcinomas. Her-2/neu was significantly expressed in low-grade gastric cancer (grade I = 50%, grade II = 34.5%, grade III = 14.5%; P = 0.030). Although there was insignificant difference between Her-2/neu over expression and other variables, Her-2/neu score 3+ was predominantly seen in females, age >60 years, Laurens intestinal type, and IIIC stage tumors.Conclusion:Her-2/neu is over-expressed in a limited group of gastric cancer patients in our population and indicates a significant strong association with low grades of gastric cancer.

Expression of Estrogen Receptors (ER), Progesterone Receptors (PR) and HER-2/neu receptors in Endometrial Carcinoma and their associations with histological types, grades and stages of the tumor.

Objective:To study and detect immunohistochemical expression of Estrogen Receptors, Progestrone Receptors and HER-2/neu Receptors in Endometrial Carcinoma (EC) and to find their associations with histological types, grades and stages of the tumor.Methods:A cross sectional study of one year duration from January 2016 to January 2017 was conducted at Histopathology department of Army Medical College, Rawalpindi. A non-probability purposive sampling technique was used to include 56 cases of EC. The specimens were tested for ER, PR and HER-2/neu expression using immunohistochemical analysis. Data was analyzed in SPSS and the significance of association of expression of the receptors with histological types, grades and stages of the tumor was assessed.Results:Significant association of Her-2/neu overexpression with histological types and grades of EC was seen, whereas the association of ER and PR expression with histological types, grades and stage of EC was statistically insignificant.Conclusion:It is suggested that EC showing over expression of HER2/neu with immunohistochemistry may be treated with anti HER-2/neu treatment with better chances of survival and decreased post-treatment morbidity.

Human epidermal growth factor receptor 2 neu expression in head and neck squamous cell cancers and its clinicopathological correlation: Results from an Indian cancer center.

Human epidermal growth factor receptor 2 (HER2)/neuprotooncogene (neu) is a proven molecular prognostic marker in breast, ovarian, gastric, and ovarian cancers. In head-and-neck cancers, varied expression is documented and therefore its prognostic role is debatable. To find the rate of overexpression of HER2/neu in head-and-neck cancers and to understand its prognostic role by evaluating its association with nodal stage and overall stage of the patient. A total of 70 surgically resected cases of head-and-neck cancers were evaluated for expression of HER2/neu by immunohistochemistry. Scoring was done according to the American Society of Clinical Oncologists/College of American Pathologistsguidelines for Her2/neu testing in breast cancer. Of the 70 cases studied, 57 were of oral cavity and 13 were laryngeal squamous cell cancers and 14 (20%) were Her2/neu positive. On correlating the expression of HER2/neu in T1/T2 (41 cases) versus T3/T4 (27 cases), the P value was found to be 0.8273 which was statistically insignificant. Furthermore, no statistically significant difference in expression of HER2/neu was found in between node negative and node positive cases (49 vs. 19 cases, respectively), with P = 0.512. In the current settings, HER2/neu is not found to be a prognostic marker in head-and-neck cancers. Standard immunohistochemistry staining protocols need to be established like in breast cancers to aid uniform reporting and further evaluate the role of this important protooncogene in head-and-neck cancers.

Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR mutant patients with non-small cell lung cancer.

Clinical studies have confirmed epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) used in lung cancer patients with EGFR mutations can obtain a better result, but still part of the patients with poor efficacy. EGFR mutation is highly related to female, nonsmoking and adenocarcinoma. Thus, we hypothesize that estrogen and circulating HER-2/neu protein might influence the efficacy of EGFR-TKIs in EGFR mutant patients with non-small cell lung cancer. HER-2/neu expression level of 357 eligible patients in its peripheral serum was determined using ELISA. The median progression-free survival (PFS) in five groups (premenopausal group, perimenopause group, peri to postmenopausal group, postmenopausal group and control group) was statistically difference (P = 0.025). Premenopausal group could predict the efficacy of EGFR-TKI (HR = 2.45, 95% CI = 1.42-4.23, P = 0.001). No statistical significance was found in median overall survival (OS) among five groups. Optimal diagnostic cut off value of HER-2/neu was set at 47.5 ng/ml, with P = 0.0607. As the cutoff value to 47.5 ng/ml division, concentrations and menopausal status was of no significant difference (P = 0.874). PFS of the group below 47.5 ng/ml was significantly longer than that of the group over 47.5 ng/ml (P = 0.000). HER-2/neu concentration was positively correlated with optimal efficacy (P = 0.042). HER-2/neu concentration over than 47.5 ng/ml was a risk factor of EGFR-TKI prognosis. Premenopausal status is an independent predictor of EGFR-TKI curative effect and circulating HER-2/neu protein is an independent prognostic factor in patients with advanced NSCLC.

Relationship between folate receptor alpha (FRα) with estrogen receptor, progesterone receptor, HER-2 neu expression in breast carcinoma

Relationship between folate receptor alpha (FRα) with estrogen receptor, progesterone receptor, HER-2 neu expression in breast carcinoma

In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in ErbB2 (Neu) oncogene induced mouse mammary tumors.

Overexpression of dominant oncogenes and the loss of tumor suppressor genes are basic genetic events in the acquisition of the malignant phenotype. The erb-b2 receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of human breast cancers. The StAR related lipid transfer domain containing 13 gene (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome band 13q12.3 and is frequently downregulated in human cancers, including 72% of breast cancers. It encodes a RhoGAP protein with sterile α motif (SAM) and StAR-related lipid transfer (START) domains. The objective of this study was to determine if loss of Stard13 plays a role in mammary tumor progression using transgenic mice expressing the activated ErbB-2 (Neu) oncogene and Cre recombinase (NIC) in mammary epithelium under transcriptional control of the murine mammary tumor virus (MMTV) promoter (MMTV-NIC). These mice were crossed with a conditional Stard13 knockout mouse (floxed exon 3), resulting in simultaneous Neu expression and Stard13 deletion, specifically in the mammary epithelium. We found that loss of Stard13 did not alter tumor growth nor significantly modify overall survival and tumor free survival. However, there was an increase in the total number of lung metastases in the Stard13 heterozygous or homozygous mice compared with the parental MMTV-NIC strain. Altogether our results indicate that Stard13 acts as a metastasis suppressor rather than a tumor suppressor gene, in Neu oncogene induced mammary tumorigenesis.

The reliability of assessment of Ki-67 and HER-2/neu expression on breast carcinoma agarose cell blocks

Background Assessment of multiple prognostic and/or predictive biomarkers in patients with breast cancer with good reliability and reproducibility using samples obtained by fine-needle aspiration (FNA) can be of significant clinical value. Objective The objective of this study was to determine the reliability of assessment of breast carcinoma markers, Ki-67 and HER-2/neu, on agarose cell blocks (CBs). Patients and methods FNA samples were obtained from 29 female patients presenting with primary breast carcinoma. To prepare CBs (cytoblocks), cells were fixed in 10% neutral formalin for 6–12 h, embedded in 2% agarose gel, processed using standard laboratory protocol for biopsy tissue, and paraffin-embedded. The expression of Ki-67 and HER-2/neu was evaluated by immunohistochemistry (IHC) on cytoblocks and their corresponding formalin-fixed, paraffin-embedded histological resection specimens. Results Tissue sections exhibited high Ki-67 expression in 27/29 (93.1%) invasive breast carcinoma cases, whereas 2/29 (6.9%) tumors revealed low Ki-67 immunoreactivity. MIB-1-stained CBs showed high Ki-67 expression in 24/29 (82.7%) breast carcinoma cases, whereas 5/29 (17.3%) tumors revealed low expression. MIB-1 IHC staining on agarose CBs showed 26/29 (89.6%) tumors correlation with tissue results. IHC analysis of HER-2/neu protein expression on tissue sections revealed that 23/29 (79.3%) breast carcinoma cases were negative for overexpression (score 0 or 1+) and 6/29 (20.7%) were positive for overexpression (3+). On agarose CBs, 21/29 (72.4%) invasive breast carcinoma tumors were negative (0 or 1+) for HER-2/neu overexpression, 2/29 (6.9%) showed equivocal IHC staining (2+), and 6/29 (20.7%) tumors were positive (3+). IHC staining for HER-2/neu on agarose CBs showed 93.1% correlation with tissue results. Conclusion In invasive breast carcinoma, Ki-67 and HER-2/neu (negative/positive) expression could be determined with good reliability on agar CBs prepared from FNA using standard IHC procedures.

Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a systematic review and meta-analysis.

This study aimed to conduct a meta-analysis to investigate the association between human epidermal growth factor receptor 2 (HER-2/neu) expression and survival in patients with epithelial ovarian cancer (EOC). HER-2/neu is one of the most frequently studied molecular biological parameters in EOC, but its prognostic impact has not been fully assessed. PubMed and Embase were searched for studies that reported HER-2/neu expression and survival in patients with EOC. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Hazard ratios (HRs) with 95% confidence interval (CI) were determined using Mantel–Haenszel random-effects model. Publication bias was investigated using funnel plots and Egger’s test. A total of 56 studies (N=7212) were included in the analysis. The results showed that patients possessing HER-2/neu expression had significant disadvantages in OS (HR = 1.41; 95%CI, 1.31 to 1.51; P < 0.001) and PFS (HR = 1.38; 95% CI, 1.23–1.56; P < 0.001). The trim-and-fill method, Copas model, and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. The present study findings provided further indication that HER-2/neu expression in patients with EOC has an adverse impact on OS and PFS.

Immunohistochemical and Clinicopathological Factors Associated with Axillary Lymph Node Metastasis in Breast Cancer Patients of Northern Pakistan

Background: Breast cancer is the most common type of tumors in Pakistani women, with axillary lymph node (ALN) positivity reported to be one of the most important prognostic factors.This study shows the distribution of various clinical and pathological variables including age, tumor size, grade, histologic subtype, and hormone receptor status among Pakistani women with and without ALN metastasis.Materials and Methods: A total of 245 cases of primary breast cancer from Northern Pakistan were analyzed in this study. Their clinical, pathological and immunohistochemical parameters, including estrogen receptor (ER), progesterone receptor (PR) and Her-2/Neu status, were extracted from previous histopathological reports and stratified based on the occurrence of ALN metastasis. Results: Occurrence of ALN metastasis was significantly different between older age patients above 50 years and younger age patients age &lt;50 years [χ² (1, N=245) =14.6, p&lt;0.001]. There was an increased number of metastases in large sized tumors &gt;5cm in size (80%, n=60), [χ² (2, N=245) =23.1, p&lt;0.001] and tumors with higher nuclear grade III (78.4%, n=40), [χ² (1, N=245) =5.1, p=0.02]. ALN metastasis was inversely associated with expression of estrogen receptor [χ² (1, N=245) =12.5, p&lt;0.001], and progesterone receptor [χ² (1, N=245) = &lt;0.001, p=0.99], while it was directly associated with Her-2/Neu expression [χ² (1, N=245) =5.63, p=0.01]. Conclusion: In Pakistani women, ALN metastasis was significantly associated with older age, tumor size, and high-grade tumors showing Her2/Neu expression and was inversely associated with ER, PR expression in breast tumors.