• Investigative Magnetic Resonance Imaging
• /
• v.19 no.3
• /
• pp.137-145
• /
• 2015

Purpose: To investigate correlations of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2) statuses with magnetic resonance imaging (MRI) features and clinicohistological characteristics in patients with invasive lobular carcinoma (ILC). Materials and Methods: Data from 64 histologically confirmed ILCs were analyzed retrospectively. Preoperative breast MRI was reviewed for morphology and dynamic contrast-enhanced kinetics of the tumor. Pathologic reports were reviewed for ER, PR, and HER2 positivity, tumor size, lymph node metastasis, and the number of metastatic lymph nodes. Furthermore, there was an investigation of the MRI features and clinicohistologic characteristics, according to the ER, PR, and HER2 statuses. Results: A significant difference in MRI features and clinicohistological tumor characteristics were observed only in relation to PR status. Of the 64 ILCs, 10 (15.6%) were PR negative. PR negative cancers, compared with PR positive cancers, were more likely to present as non-mass enhancement (P = 0.027); have a significantly larger mean tumor size ($5.00{\pm}1.05cm$ vs. $2.57{\pm}0.21cm$, P = 0.021); and have significantly more metastatic lymph nodes (P = 0.010). Conclusion: PR negative ILC presented more frequently as non-mass enhancement on MRI, with larger tumors and increased numbers of metastatic lymph nodes. Therefore, the PR status plays an important role in determining MRI features and clinicohistological characteristics of ILC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1077-1082
• /
• 2016

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

• Parasites, Hosts and Diseases
• /
• v.55 no.5
• /
• pp.491-503
• /
• 2017

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine ($5{\mu}M$) at $20{\mu}M$ and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at $1-5{\mu}M$, but host cells were destroyed at $10-20{\mu}M$. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

• Radiation Oncology Journal
• /
• v.30 no.3
• /
• pp.124-131
• /
• 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.

• Annals of Occupational and Environmental Medicine
• /
• v.34
• /
• pp.5.1-5.10
• /
• 2022

Background: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data. Case presentation: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer. Conclusions: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.3
• /
• pp.245-249
• /
• 2008

Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids and has a potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(epidermal growth factor receptor, EGFR). Pleomorphic adenoma is the most common salivary benign tumor and histologically, it contains the epithelial cell, the myo-epithelial cell and mesenchymal ingredient, which is various aspect. Adenoid cystic carcinoma is an infiltrative malignant salivary gland tumor with three different histological patterns: cribriform, tubular or solid. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. In this study, we used an immunohistochemical technique to investigate the expression of EGF in 6 specimens of adenoid cystic carcinoma and 10 specimens of pleomorphic adenoma taken from patients treated at Dept. of Oral and Maxillofacial Surgery, Dankook University. The results were as follows. 1. In pleomorphic adenoma, ductal structure and scattered spindle cells in hyalinized stroma, disclosing myxoid stroma and hyalin, cartilage formation were observed. Immunohistologically, weak EGF expression in ductal structure and negative in stromal area were observed. 2. Cribriform type of adenoid cystic carcinoma showed numerous pseudocyst surrounded by dark small neoplastic cells in the back-ground of fibrous connective tissue and moderate EGF expression of dark cells adjacent to pseudo lumen in cribriform pattern, while weak expression in other most cells. 3. Tubular type of adenoid cystic carcinoma showed numerous ductal pattern surrounded by two layered neoplastic cells in the back-ground of fibrous connective tissue and strong EGF expression in luminal cells of ductal structure, while weak expression in outer cells. From the results obtained, we suggest that EGF is mainly biosynthesized in cells forming duct like structures of tubulo-ductal type or cribriform adenoid cystic carcinoma and it may play a role, as a cell mitogen in adenoid cystic carcinoma growth.

• Biomedical Science Letters
• /
• v.24 no.1
• /
• pp.9-14
• /
• 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
• /
• v.17 no.4
• /
• pp.1973-1978
• /
• 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.

• Journal of Gastric Cancer
• /
• v.14 no.3
• /
• pp.180-186
• /
• 2014

Purpose: At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab ($Herceptin^{(R)}$; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection. Materials and Methods: A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results: The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor. Conclusions: HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.

• Journal of Gastric Cancer
• /
• v.21 no.2
• /
• pp.191-202
• /
• 2021

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K_D=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K_D=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.