• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5773-5777
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• 2015

Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.295-298
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• 2016

Background: Breast cancer is a very common health problem in Iranian women. The HER2-neu gene is a transmembrane receptor tyrosine kinase with homology to members of the EGF receptor family. The aim of this study was to investigate the association between HER2-neu oncogene status with prognostic factors of breast cancer in Kermanshah province, Iran. Materials and Methods: Relationship between HER2-neu and prognostic factors of 130 cases of breast cancer were evaluated during two years in Imam Reza hospital in Kermanshah, Iran. Data were analyzed using descriptive statistics and the T-test and Mann-Whitney U non-parametric test using SPSS 19. Results: The mean age for the patients was $46.0{\pm}8.0years$, all being female. Among the predictive factors for breast cancer were family history, stage of disease, involvement of the lymphovascular system, number of involved lymph nodes in axillaries, grading and hormone receptor status with HER2-neu oncogene had direct correlation and between factors, tumor location, patient age and histological characteristics and HER2-neu oncogene had no significant relationship. We found significant correlation between HER2 with ER and PR and also HER2 with ER, PR negative. Conclusions: HER2-neu is risk factor that can be a good prognostic and also predictive factor. For these reasons, we recommend that it be evaluated for all types of BC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3363-3367
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• 2016

Background: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. Materials and Methods: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER-2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. Results: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. Conclusions: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER-2 positive tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.421-425
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• 2015

Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age $57.9{\pm}19.5years$ were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/neu was negative in 97.5% of patients with IHC and in 100% of patients with CISH technique. Only one case (2.5%) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47% of cases were in Clark level III, while the mean of Breslow thickness was $3.56{\pm}2.87mm$. The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.90-94
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• 2014

Salivary duct carcinoma(SDC) is rare malignancy, accounting for approximately 1-3% of all malignant salivary gland tumors. Systemic chemotherapy has been used for stage IV SDC, but there is no consensus on the standard treatment. SDC is histologically similar to ductal carcinoma of breast and often overexpress HER2/neu, hence HER2/neu targeted therapy could be one of treatment options. A 75-year-old Arabian man was diagnosed as SDC of right parotid gland with extensive metastases. He received oral 5-FU as palliative chemotherapy, but he was intolerable to oral chemotherapy due to severe oral mucositis. Considering immunohistochemical stain of tumor tissue showing strong positive for HER2/neu, we decided to administer an anti-HER2/neu antibody, trastuzumab. Follow-up CT scans before the third dose of trastuzumab demonstrated remarkable regression of multiple metastases as well as primary tumor. This case suggests that HER2/neu targeted therapy may be a potential therapeutic option for the SDC patient with overexpression of HER2/neu.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4353-4358
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• 2013

Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5551-5556
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• 2014

Background: The prognostic value of human epidermal growth factor receptor-2 (HER-2/neu) for survival of patients with colorectal cancer (CRC) is still ambiguous. We therefore performed a meta-analysis to evaluate its prognostic significance. Materials and Methods: We searched the MEDLINE and EMBASE databases for published literature investigating associations between HER-2/neu status and overall survival of patients with CRC. A meta-analysis was performed using a DerSimonian-Laird model and publication bias was investigated by Begg's and Egger's tests. Subgroup analysis was also conducted according to the study design type, study quality score, cut-off value for HER-2/neu overexpression, publication region, patient number and publication year. Results: A total of 17 eligible studies involving 2,347 patients were identified for this meta-analysis. The combined hazard ratio (HR) was 1.31 (95% confidence interval (CI): 0.96-1.79), suggesting that HER-2/neu overexpression was not significantly associated with overall survival of patients with CRC. However, subgroup analysis revealed that HER-2/neu overexpression had an unfavorable impact on survival when the analysis was restricted to subgroups of study quality score ${\leq}5 $(HR=1.56, 95%CI: 1.17-2.10), Asian patients (HR=1.74, 95%CI: 1.22-2.49), patient number ${\leq}106$ (HR=1.57, 95%CI: 1.01-2.44), publication year before 2003 (HR=1.59, 95%CI: 1.02-2.49), and prospectively designed study (HR=3.62, 95%CI: 1.42-9.24). The effect disappeared in subgroups of study quality scores > 5 (HR=0.69, 95%CI: 0.33-1.44), non Asian patients (HR=1.14, 95%CI: 0.77-1.70), patients' number > 106 (HR=1.07, 95%CI: 0.67-1.72), publication year after 2003 (HR=1.13, 95%CI: 0.76-1.69), and retrospectively designed study (HR=1.22, 95%CI: 0.89-1.67). Conclusions: Our meta-analysis suggests that HER-2/neu overexpression might not be a significantly prognostic indicator for patients with CRC. Further studies are required to confirm these results.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.307-315
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• 2004

Purpose: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in korean patients. Materials and Methods: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Results: Proportion of the COX-2 expression in total patients was $27.6\%$. The percentage of tumors that stained positive for COX-2 in korean and Caucasian women with early-onset breast carcinoma were $37.9\%$ and $20.8\%$, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was $67.9\%$, compared to $81.9\%$ of the COX-2 negative patients and the result was statistically not significant. Conclusions : A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including radiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

• Journal of Life Science
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• v.18 no.1
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• pp.16-22
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• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2231-2235
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• 2013

Background: Categorizing breast tumors based on the ER, PR and HER/Neu 2 receptor status is necessary in order to predict outcome and assist in management of breast cancer. Herfe we assessed this question in South Indian patients. Materials and Methods: A total of 619 formalin fixed paraffin embedded breast tumor tissues were collected from pathology archives after receipt of ethical clearance. With the help of primary and secondary conjugated antibodies, expression status of ER, PR and HER2/neu was determined. All the experimental data were assessed for correlations with histopathological features of tumors and clinical presentation of the subjects. Results: In the present study, the ages ranged from 20-87 years with a mean of $50.0{\pm}12.q$ years, and majority of the tumors (84%) were of infiltrating duct cell carcinoma type. Assessment of ER, PR and Her-2/neu expression showed that 46% were triple negative. Interestingly, an inverse relation between ER, PR and HER-2/neu was apparent in 41.2% (p<0.0001) of the tumors, of which 24.5% (p<0.0001) were ER and PR co-negative but HER-2 positive. Conclusions: ER and PR positive tumors are less common (i.e<30%) compared to HER-2/neu positive tumors (i.e>50%) in Indian breast cancer patients, underlining the need for effective diagnostic screening and specific therapeutic managements in order to improve the survival rate of patients in low resource countries such as India.