• 생명과학회지
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• 제18권1호
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• pp.16-22
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• 2008

개에서의 유선 종양진단은 총 49 case 중에서 Human epidermal growth factor receptor (HER-2/neu, c-erbB-2), Epidermal growth factor receptor (EGFR), Activated leukocyte cell adhesion molecule (ALCAM) 등 면역조직화학적염색법을 실시하였다. 우선 49 case를 두 그룹으로 즉: 양성종양그룹 (22 case)과 악성종양그룹 (27 case)으로 구분하였다. 면역조직화학적염색법의 분석결과 HER-2/neu의 발현은 양성종양에서는 31.8% (7/22), 악성종양에서는 29.6% (8/27)의 발현율을 보였고, EGFR의 발현은 양성종양에서는 27.3% (6/22), 악성종양에서는 22.2% (6/27)의 발현율을 보였으며, ALCAM의 발현은 양성종양에서는 40.9% (9/22), 악성종양에서는 7.4% (2/27)의 발현율을 보였다. 결론적으로 개에서의 유선종양진단의 발현율은 사람에서 보고된 것($25%{\sim}30%$)과 비슷하게 나타났으며 임상진단분야에서 HER-2/neu항체로 개에서의 유선종양진단에서 유용한 평가수단으로 적용될 수 있으리라 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10277-10280
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• 2015

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3903-3909
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• 2016

Purpose: To evaluate the expression of Her2/neu and Ki-67 in benign and malignant gallbladder lesions, and to establish correlations with clinico-pathologic parameters. Materials and Methods: A retrospective analysis was conducted on formalin fixed paraffin embedded (FFPE) benign (n=25) and malignant gallbladder (n=25) tissue samples. Hematoxylin and eosin stained slides of each case were reviewed for: type of malignancy (whether adenocarcinoma, squamous cell carcinoma, or any other type), grade (well, moderate, and poor), depth of invasion, pre-neoplastic changes in adjacent mucosal epithelium like metaplasia and dysplasia. Immunohistochemistry for Her 2 neu and Ki-67 was performed and data analysis was conducted using SPSS 17 software. Chi-square test was used to compare categorical/dichotomous variables. P value of ${\leq}0.05$ was considered significant. Results: The difference of Her 2 neu expression and Ki67 index between benign and malignant groups was found to be statistically significant. Her2/neu positivity did not have any significant correlation with various clinicopathological parameters other than liver involvement. 5 cases of gallbladder cancer showed both Her2/neu and Ki67 positivity. Ten cases were Ki67 positive but Her2/neu negative while one case was Her2/neu positive but Ki67 negative. Conclusions: The present study demonstrated overexpression of Her2/neu and Ki67 in gallbladder cancer. A trend of decreasing Her2/neu expression with increasing grade of tumor was observed. Furthermore, greater Ki67 positivity was found in cases with lymph node metastasis and distant metastasis. Future studies with a larger number of patients will be required to precisely define the correlation of Her2/neu expression and Ki67 positivity with clinicopathological parameters. The results however are encouraging and suggest evaluation of Her2/neu as a candidate for targeted therapy.

• Natural Product Sciences
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• 제26권4호
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• pp.345-350
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• 2020

In recent years, tyrosine kinases (TKs) have been the target to combat cancers, and most of the developed inhibitors are of synthetic origin. Natural compounds that have the properties as the TK's inhibitors are very limited. This paper described the isolation of a new dammarane triterpene from the tree bark of Sandoricum koetjape, along with three known related dammaranes from the damar resin of Shorea javanica, as well as their inhibitory properties against eight receptor TKs (RTKs: EGFR, HER2, HER4, IGF1R, InsR, KDR, PDGFRα, and PDGFRβ). Based on the NMR and mass spectral data the new compound was identified as (12β,20S)-12,20-dihydroxy-3,4-seco-dammaran-4,24-dien-3-oic acid (12β-hydroxydammarenolic acid) (1), while the three known compounds were identified as (20S)-20-hydroxy-3,4-seco-dammaran-4,24-dien-3-oic acid (dammarenolic acid) (2), (3β,20S)-3,20-dihydroxydammaran-24-ene (3), and (20S)-3-oxo-20-hydroxydammaran-24-ene (4). The tyrosine kinase assay of the four compounds resulted only 1 and 2 at concentration of 10 μM that had weak activity against EGFR and InsR, with their % inhibitory were 30%, 27% (1), 45%, and 32% (2), respectively. The results suggested that the presence of a linear carboxylic acid group in both compounds could be of significance to the inhibitory properties against the two RTKs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1019-1024
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• 2015

Background: Survival of breast cancer patients depends on a number of factors which are not only prognostic but are also predictive. A number of studies have been carried out worldwide to find out prognostic and predictive significance of different clinicopathological and molecular variables in breast cancer. This study was carried out at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, to find out the impact of different factors on overall survival of breast cancer patients coming from Northern Pakistan. Materials and Methods: This observational retrospective study was carried out in the Oncology Department of NORI Hospital. A total of 2,666 patients were included. Data were entered into SPSS 20. Multinomial logistic regression analysis was performed to determine associations of different variables with overall survival. P values <0.05 were considered significant. Results: The mean age of the patients was 47.6 years, 49.5% being postmenopausal. Some 1,708 were ER positive and 1,615 were PR positive, while Her 2 neu oncogene positivity was found in 683. A total of 1,237 presented with skin involvement and 426 had chest wall involvement. Some 1,663 had > 5cm tumors. Lymph node involvement was detected in 2,131. Overall survival was less than 5 years in 669 patients, only 324 surviving for more than 10 years, and in the remainder overall survival was in the range of 5-10 years. Conclusions: Tumor size, lymph node metastases, receptor status, her 2 neu positivity, skin involvement, and chest wall involvement have significant effects whereas age and menopausal status have no significant effect on overall survival of breast cancer patients in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.807-812
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• 2014

Background: The clinical course of the neoplasm may vary due to both patient and tumor cell characteristics. Aim: The aim of this study was to research the influence of certain clinical and pathological features on the prognosis of early stage breast cancer. Materials and Methods: This study included 117 women that were treated and followed-up in between the years 2001-2011. The demographic, clinical and histopathological features of the cases were reviewed retrospectively. Statistical analysis: In categorical comparisons between groups, cross-tab statistics were provided and significance levels were estimated using chi-square test. Cox regression analysis, Pearson and Spearman correlation tests, and the Kaplan-Meier test were also used. Results: With an average of 35-months follow-up, the mean disease-free survival of patients was 91 months and the mean overall survival time was 132 months. In the whole study group, the disease-free survival rates were 88, 84, 83 and 52%, while the overall survival rates 95, 94, 83, and 83% within the first, third, fifth and tenth years, respectively. The disease-free and overall survival rates were decreased with increasing tumor grades, though this was not statistically significant. The presence of lymphovascular invasion, positive staining with Ki67 and postmenopausal status were associated with shorter disease-free and overall survival times. In multivariate analysis, only age and Her2/neu receptor status influenced the prognosis significantly. Conclusions: In parallel to clinical, histopathological, and immunohistochemical prognostic features in breast cancer, in this study positive Her2/neu receptor status, a previously accepted poor prognostic factor, was found to have positive influence after trastuzumab treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2591-2600
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• 2015

Breast cancer is the most common cancer worldwide among women and the second most common cancer. Approximately 15-23% of breast cancers over-express human epidermal growth factor receptor2 (HER2), a 185-kDa transmembrane tyrosine kinase, which is mainly found at the cell surface of tumor cells. HER2-positive breast cancer, featuring amplification of HER2/neu and negative expression of ER and PR, has the three following characteristics: rapid tumor growth, lower survival rate, and better response to adjuvant therapies. Clinically, it is notable for its role in a pathogenesis that is associated with increased disease recurrence and acts as a worse prognosis. At the same time, it represents a good target for anti-cancer immunotherapy despite the prevalence of drug resistance. New treatments are a major topic of research, and a brighter future can be expected. This review discusses the role of HER2 in breast cancer, therapeutic modalities available and prognostic factors.

• 대한의생명과학회지
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• 제21권1호
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• pp.23-31
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• 2015

Recently, specific antibodies have been used extensively to diagnose and treat various diseases. It is essential to assess the efficacy and specificity of antibodies, especially the in vivo environment. Anti-HER-2/neu mAb was evaluated as a possible transporting agent for radioimmunotherapy. The monoclonal antibody was successfully radio-labeled with $^{131}I$. In vitro binding assays were performed to confirm its targeting ability using another radio-iodine, $^{125}I$. Binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in HER-2/neu expressing CT-26 cells was found to be 4.5%, whereas the binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in wild-type CT-26 was only 0.45%. In vivo images were obtained and analyzed through $\gamma$-camera and an optical fluorescent modality, IVIS-200. $\gamma$-camera images showed that $^{131}I$ labeled anti-HER-2/neu mAb accumulated in HER-2/neu CT-26 tumors. Optical imaging based on near infrared fluorescence labeled anti-HER-2/neu mAb showed higher fluorescence intensities in HER-2/neu CT-26 tumors than in wild-type CT-26 tumors. Anti-HER-2/neu mAb was found to specifically bind to its receptor expressing tumor. Our study demonstrates that in vivo imaging technique is a useful method for the evaluation of an antibody's therapeutic and diagnostic potentials.

• Journal of Breast Disease
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• 제6권2호
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• pp.52-59
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• 2018

Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.