• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3937-3940
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• 2013

Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4119-4123
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• 2012

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6397-6403
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• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5557-5563
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• 2014

Background: This study investigated the survival benefit of radiotherapy (RT) of the supra- and infraclavicular lymphatic drainage area in Chinese women with T1-2N1M0 breast cancer receiving mastectomy. Methods: A total of 593 cases were retrospectively reviewed from 1998 to 2007. The relationship between supra- or infraclavicular fossa relapse (SCFR) and post-operative RT at the supra-/infraclavicular lymphatic drainage area was evaluated. Results: The majority of patients (532/593; 89. 8%) received no RT while 61 patients received RT. The median follow-up was 85 months. Among patients without RT, 54 (10. 2%) developed recurrence in the chest wall or ipsilateral SCFR. However, none of the 61 patients who underwent RT demonstrated SCFR. One patient who received RT (1. 6%) experienced recurrence in the chest wall. Univariate analysis revealed that age and molecular subtype (both P < 0. 05) were two prognostic factors related to supraclavicular and infraclavicular fossa relapse-free survival (SFRFS). Multivariate analysis revealed that only Her-2 positive status (P = 0. 011) was an independent predictor of SFRFS. RT had no influence on distant metastasis (P = 0. 328) or overall survival (P = 0. 541). SCFR significantly affected probability of distant metastasis (P < 0. 001) and overall survival (P < 0. 001). Conclusion: Although RT was not significantly associated with SFRFS, postoperative RT was significantly associated with a lower locoregional (i. e., supraclavicular/infraclavicular and chest wall) recurrence rate. SCFR significantly influenced distant metastasis-free survival, which significantly influenced the overall survival of T1-2N1M0 breast cancer patients after mastectomy. Thus, prophylactic RT is recommended in T1-2N1M0 breast cancer patients, especially those who have Her-2 positive lesions.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.233-240
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• 2021

Evaluation of the resected margins of the frozen section during breast-conserving surgery can determine the presence of cancer cells in a short time and have a significant impact on the scope of surgery and the prognosis of the patient. However, breast tissue is composed of adipose tissue, which affects the accuracy of the test. In this study, a new method was applied to the resected surface of the frozen section in which wiping the surface of the frozen section block with alcohol was expected to expose the parenchyma to the surface as the adipose tissue would melt momentarily. Indeed, of the total of 98 cases, 37 cases showed a better exposure ratio of the parenchyma in the improved frozen section test than in the previous frozen section test. Of the 37 cases with increased visibility of parenchymal sections obtained by this method, two cases of ductal carcinoma in situ (DCIS) were detected. Although there are limitations such as turnaround time (TAT), the diagnostic accuracy of histopathologic examination of the frozen section may improve through this method and may have a direct impact on patient safety, and should therefore be researched further.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Journal of the Korean Society of Radiology
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• v.83 no.1
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• pp.149-161
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• 2022

Purpose To investigate the correlation between computer-aided diagnosis (CAD) parameters in 3-tesla (T) MRI and pathologic immunohistochemical (IHC) markers in invasive carcinoma of no special type (NST). Materials and Methods A total of 94 female who were diagnosed with NST carcinoma and underwent 3T MRI using CAD, from January 2018 to April 2019, were included. The relationship between angiovolume, curve peak, and early and late profiles of dynamic enhancement from CAD with pathologic IHC markers and molecular subtypes were retrospectively investigated using Dwass, Steel, Critchlow-Fligner multiple comparison analysis, and univariate binary logistic regression analysis. Results In NST carcinoma, a higher angiovolume was observed in tumors of higher nuclear and histologic grades and in lymph node (LN) (+), estrogen receptor (ER) (-), progesterone receptor (PR) (-), human epidermal growth factor 2 (HER2) (+), and Ki-67 (+) tumors. A high rate of delayed washout and a low rate of delayed persistence were observed in Ki-67 (+) tumors. In the binary logistic regression analysis of NST carcinoma, a high angiovolume was significantly associated with a high nuclear and histologic grade, LN (+), ER (-), PR (-), HER2 (+) status, and non-luminal subtypes. A high rate of washout and a low rate of persistence were also significantly correlated with the Ki-67 (+) status. Conclusion Angiovolume and delayed washout/persistent rate from CAD parameters in contrast enhanced breast MRI correlated with predictive IHC markers. These results suggest that CAD parameters could be used as clinical prognostic, predictive factors.

• Proceedings of the Korean Information Science Society Conference
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• 1999.10b
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• pp.422-424
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• 1999

본 논문에서는 질감 특징과 신경회로망을 이용한 유방암조직영상의 분할 방법을 제안한다. 신경회로망의 입력 노드에 사용될 질감 특징을 얻기 위해 10개의 영상에 대해 각 영역(양성세포핵, 음성세포핵, 배경)에서 10개씩의 화소를 선택하고, 그 화소를 중심으로 하는 5$\times$5 영역 30개를 획득, 총 300개의 영역에 대해 R, G, B 각각의 밴드에서 18개의 질감특징을 추출한다. 54개의 입력노드, 28개의 은닉노드, 3개의 출력노드의 구조를 가진 신경회로망을 구성하고, 역전파 학습 알고리즘을 사용하여 신경회로망을 최대오차율이 10-3보다 작을 때까지 학습시킨다. 학습에 의해 획득되어진 분류기를 이용하여 유방암 조직 세포영상을 양성세포핵, 음성세포핵, 배경부분으로 자동 분할한다.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.13-20
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• 1997

관상피내암종의 조직학적 분류에 있어서 그 기준으로써 공통적으로 사용된 소견은 핵등급, 면포형 괴사 및 성장유형이었다. 그러나 최근의 분류(Tavassoli, 1992; Tavassoli and Man, 1995; Poller 등, 1994; Holland 등, 1994; Silverstein 등, 1995; Millis, 1996)에서는 핵등급과 면포형 괴사만을 분류의 기준으로 사용하고 있고 성장유형은 포함시키지 않는 경향이 있는 것 같다. 이는 관상피내암종의 성장유형은 너무나 다양하고 혼합형으로 자라는 경우가 많아 관찰자간의 재현성이 떨어지고, 이와 반대로 핵등급이나 면포형 괴사는 관찰자간의 재현성이 비교적 높을 뿐만 아니라 여러 가지 생물학적 표지자와도 관련이 잘 지워지기 때문으로 생각한다. 관상피내암종의 분류나 등급매김에 있어서는 연구자마다 사용하는 용어가 다르고 그들이 정한 등급의 기준이 서로 다르나 대체로 세 등급으로 나뉘어짐을 알 수 있었다. 한편, 국내에서는 유방의 관상피내암종에 대한 연구가 미흡한 실정이므로 이에 대한 지속적인 자료의 축적과 연구가 필요하리라 생각한다.