• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10607-10611
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• 2015

Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05).Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1015-1018
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• 2016

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.329-337
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• 2012

Considerable attention has been given to the accuracy of HER-2 testing and the correlation between the results of different testing methods. This interest reflects the growing importance of HER-2 status in the management of patients with breast cancer. In this study the detection of HER-2 gene and centromere 17 status was evaluated using dual-colour primed in situ labelling (PRINS) in comparison with fluorescence in situ hybridization (FISH). These two methods were evaluated on a series of 27 formalin fixed paraffin embedded breast carcinoma tumours, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+/0, 2+ and 3+). HER-2 gene amplification (ratio${\geq}2.2$) by PRINS was found in 3:3, 6:21 and 0:3 in IHC 3+, 2+ and 1+/0 cases, respectively. Comparing FISH and IHC (immunohistochemistry), showed the same results as for PRINS and IHC. Chromosome 17 aneusomy was found in 10 of 21 IHC 2+ cases (47.6%), of which 1 (10%) showed hypodisomy (chromosome 17 copy number per cell${\leq}1.75$), 7 (70%) showed low polysomy (chromosome 17 copy number per cell=2.26 - 3.75) and 2 (20%) showed high polysomy (chromosome 17 copy number per cell ${\geq}3.76$). The overall concordance of detection of HER-2 gene amplification by FISH and PRINS was 100% (27:27). Furthermore, both the level of HER-2 amplification and copy number of CEN17 analysis results correlated well between the two methods. In conclusion, PRINS is a reliable, reproducible technique and in our opinion can be used as an additional test to determine HER-2 status in breast tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.459-462
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• 2012

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

• Biomedical Science Letters
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• v.24 no.1
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• pp.9-14
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• 2018

Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

• 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.

• Journal of English Language & Literature
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• v.64 no.2
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• pp.239-252
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• 2018

Many critics on William Faulkner's As I Lay Dying have read Addie Bundren as the disrupter of patriarchal power. By raising a question about the usefulness of language, which is the symbolic power of patriarchy and having an affair with the preacher Whitfield outside her wedlock, Addie directly challenges patriarchal power. From a quite different vantage point, however, we can read Addie as the faithful protector of the norm of whiteness in the South in light of the social hierarchy. As a former school teacher, Addie is from middle class before her marriage. By her marriage to Anse, who is a lower-class white, Addie has class anxiety that her social status in the stratum of whiteness could be degraded from a middle to a lower-class white, "white trash," which means that she is not white enough to be considered as the normative whiteness. Especially, Addie's anxiety increases due to the fact that her lazy husband is reluctant to work and relies on her neighbors, causing her family to be entrapped at the bottom in the stratum of whiteness. Therefore, she decides to take revenge on her husband after giving birth to her second child Darl by asking Anse to bury her dead body in her familial burial site in Jefferson. By rendering her family to suffer the hardship during her funeral procession, not only does she succeed in taking revenge on Anse on the surface, she regains her social status as a middle-class white by being buried in Jefferson fundamentally.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7695-7700
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• 2015

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2555-2558
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• 2016

Background: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. Materials and Methods: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+were considered positive. Results: Our study included 103 cases (66 males and 37 females) with a mean age of $65.1{\pm}14.8$ years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older ($70.6{\pm}19.3$ years old) than the negative cases ($64.2{\pm}13.8$, p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). Conclusions: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis.