• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4113-4117
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• 2012

Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the $ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with $ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients. $ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between $ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that $ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7597-7602
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• 2014

Background: Amplification and overexpression of human epidermal growth factor receptor 2 (HER2/neu) oncogene has considerable prognostic value in breast and gastric cancers. This study aimed to evaluate the frequency, overexpression pattern, clinical significance, and concordance between the results for protein expression and gene amplification of HER-2/neu in gastric and gastro-esophageal junction carcinomas. Materials and Methods: In this study, 101 gastric tissue samples which were included in tissue microarray were immunohistochemically examined for overexpression of HER2/neu. Chromogenic in situ hybridization (CISH) was used for HER-2/neu amplification. The correlation of HER2/neu amplification with clinicopathological parameters was also assessed. In addition, concordance between CISH and IHC was detected. Results: This study demonstrated a significant difference in the overexpression of HER2/neu in gastric tumors. The overexpression of HER2/neu was significantly higher in intestinal type, poorly differentiated grade, large size ($5cm{\leq}$) and positive nodal involvement tumors (p-value=0.041, 0.015, 0.038 and 0.071, respectively). Also, amplification of HER2/neu according to CISH test, had a significant positive correlation with tumor size and tumor type (p-value=0.018 and 0.058, respectively).Concordance between CISH and IHC was 76.9% in 101 evaluable samples. Conclusions: IHC/CISH differences were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumor heterogeneity in gastric cancers compared to breast cancers. Therefore, this can be a potential marker for targeted therapy of malignant gastric tumors.

• Radiation Oncology Journal
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• 제30권3호
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• pp.124-131
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• 2012

Purpose: To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Materials and Methods: Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Results: Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05). Conclusion: We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4863-4867
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• 2015

Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5081-5084
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• 2015

Background: Breast cancer is a malignant tumor that starts from cells of the breast and is seen mainly in women. It's the most common cancer in women worldwide and is a major threat to health. The purpose of this study was to fit a Cox proportional hazards model for prediction and determination of years of survival in Iranian patients. Materials and Methods: A total of 366 patients with breast cancer in the Cancer Research Center were included in the study. A Cox proportional hazard model was used with variables such as tumor grade, number of removed positive lymph nodes, human epidermal growth factor receptor 2 (HER2) expression and several other variables. Kaplan-Meier curves were plotted and multi-years of survival were evaluated. Results: The mean age of patients was 48.1 years. Consumption of fatty foods (p=0.033), recurrence (p<0.001), tumor grade (p=0.046) and age (p=0.017) were significant variables. The overall 1- year, 3-year and 5-year survival rates were found to be 93%, 75% and 52%. Conclusions: Use of covariates and the Cox proportional hazard model are effective in predicting the survival of individuals and this model distinguished 4 effective factors in the survival of patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6425-6428
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• 2014

Background: Prostatic adenocarcinoma is one of the main causes of cancer death, and its timely diagnosis and preventing its progression dramatically helps improve life indexes. Given the high disease recurrence rate, today, research is more inclined toward exploring causes of recurrence and development, and innovation of modern treatment methods. Several studies have explored over-expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic cancer so far, with different results. Thus, it was decided to investigate HER-2/neu overexpression in patients with prostatic adenocarcinoma in Iran. Materials and Methods: A sample size of 40 patients with prostate cancer entered the study, using a cross-sectional, non-randomized sampling method. Parameters studied included patient age at surgery, Gleason score, serum prostatic specific antigen (PSA) before surgery, and positive sample rate after immunohistochemical staining to investigate HER-2/neu overexpression. Results: In terms of HER-2/neu receptor staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and 4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of age, an inverse correlation was found (-0.181), but without significance (p=0.263). In terms of serum PSA, the correlation coefficient was 0.449 (p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240). Conclusions: In this study, HER-2/neu overexpression occurred in 27.5% of prostate cancer cases, which is a relatively high figure, compared to similar studies elsewhere. While, we failed to reveal any relationship between HER-2/neu expression status with progression and prognosis of disease, it was demonstrated that the serum PSA level was significantly higher in cases with increased receptor expression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3555-3559
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• 2014

Background: The triple-negative breast cancer (TNBC) is an aggressive cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Preoperative mammography and ultrasound features of TNBC may potentially suggest characteristics of the disease and assist in treatment decisions. Materials and Methods: The study covered 153 patients with TNBC from May 2011 to May 2012 who were confirmed by postoperative pathology results in our hospital. We compared the radiological findings among the patients and sought to determine the significant iconographic features. The biomarkers p53 and Ki-67 are regarded as significant factors in TNBC. They were therefore used to divide the TNBC into four groups for assessment of relationships with TNBC imaging features. Results: On mammography, most TNBCs exhibit obscure (44.3%) masses. On ultrasound, the majority of masses (95.4%) were predominantly indistinct (50.7%), irregular (76.0%) or featuring posterior echo enhancement/shadowing. Color Doppler flow imaging (CDFI) emphasized hypervascular (32.9%) masses. Differences in CDFI by ultrasound among the four groups were statistically significant (p=0.009). There were obvious differences in the percentages of spiculated margin (p=0.049) and intensive posterior echo (p=0.006) with spotty flow imaging by ultrasound between the Ki-67 (+) p53 (+) and other groups. Conclusions: A combination of mammography and ultrasound revealed the imaging characteristics of TNBC included an obscure mass with less attenuated posterior echoes and some vascularity. A worse prognosis was associated with spiculated margin and intensive posterior echoes with spotty flow imaging.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1973-1978
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• 2016

Background: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. Materials and Methods: Formalin-fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. Results. Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). Conclusions. The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10875-10878
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• 2015

The epidermal growth factor receptor (EGFR) is an important surface receptor with N-glycans in its extracellular domain, whose glycosylation is essential for its function, especially in tumor cells. Here, we demonstrated that polylactosamine is markedly increased in H7721 hepatocellular carcinoma cells after treatment with EGF, while it apparently declined after exposure to all-trans retinoic acid (ATRA). In the study of the enzymatic mechanism of this phenomenon, we explored changes in the expression of poly-N-acetyllactosamine (PLN) branching glycosyltransferases using RT-PCR. Among the four glycosyltransferases with altered expression, GnT-V was most elevated by EGF, while GnT-V and B3GNT2 were most declined by ATRA. Next, we conducted co-immunoprecipitation experiments to test whether B3GNT2 and EGFR associate with each other. We observed that EGFR is a B3GNT2-targeting protein in H7721 cells. Taken together, these findings indicated that the altered expression of B3GNT2 will remodel the PLN stucture of EGFR in H7721 cells, which may modify downstream signal transduction.