• Korean Journal of Radiology
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• v.20 no.1
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• pp.58-68
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• 2019

Objective: To compare digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) in the detectability of breast cancers in patients with dense breast tissue, and to determine the influencing factors in the detection of breast cancers using the two techniques. Materials and Methods: Three blinded radiologists independently graded cancer detectability of 300 breast cancers (288 women with dense breasts) on DBT and conventional FFDM images, retrospectively. Hormone status, histologic grade, T stage, and breast cancer subtype were recorded to identify factors affecting cancer detectability. The Wilcoxon signed-rank test was used to compare cancer detectability by DBT and conventional FFDM. Fisher's exact tests were used to determine differences in cancer characteristics between detectability groups. Kruskal-Wallis tests were used to determine whether the detectability score differed according to cancer characteristics. Results: Forty breast cancers (13.3%) were detectable only with DBT; 191 (63.7%) breast cancers were detected with both FFDM and DBT, and 69 (23%) were not detected with either. Cancer detectability scores were significantly higher for DBT than for conventional FFDM (median score, 6; range, 0-6; p < 0.001). The DBT-only cancer group had more invasive lobular-type breast cancers (22.5%) than the other two groups (i.e., cancer detected on both types of image [both-detected group], 5.2%; cancer not detected on either type of image [both-non-detected group], 7.3%), and less detectability of ductal carcinoma in situ (5% vs. 16.8% [both-detected group] vs. 27.5% [both-non-detected group]). Low-grade cancers were more often detected in the DBT-only group than in the both-detected group (22.5% vs. 10%, p = 0.026). Human epidermal growth factor receptor-2 (HER-2)-negative cancers were more often detected in the DBT-only group than in the both-detected group (92.3% vs. 70.5%, p = 0.004). Cancers surrounded by mostly glandular tissue were detected less often in the DBT only group than in the both-non-detected group (10% vs. 31.9%, p = 0.016). DBT cancer detectability scores were significantly associated with cancer type (p = 0.012), histologic grade (p = 0.013), T and N stage (p = 0.001, p = 0.024), proportion of glandular tissue surrounding lesions (p = 0.013), and lesion type (p < 0.001). Conclusion: Invasive lobular, low-grade, or HER-2-negative cancer is more detectable with DBT than with conventional FFDM in patients with dense breasts, but cancers surrounded by mostly glandular tissue might be missed with both techniques.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4603-4608
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• 2015

Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

• Investigative Magnetic Resonance Imaging
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• v.14 no.2
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• pp.95-102
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• 2010

Purpose : To evaluate the magnetic resonance imaging (MRI) and clinicopathological features of triple negative breast cancer, and compare them with those of non-triple negative breast cancer. Materials and Methods : This study included 231 pathologically confirmed breast cancers from January 2007 to May 2008. We retrospectively reviewed the MRI findings according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon: mass or non-mass type, mass shape, mass margin, non-mass distribution, and enhancement pattern. Histologic type, histologic grade, and the results for epidermal growth factor receptor, p53, and Ki 67 were reviewed. Results : Of 231 patients, 43(18.6%) were triple negative breast cancer. Forty triple negative breast cancers (93.0%) were mass-type lesion on MRI. A round or oval or lobular shape (p=0.006) and rim enhancement (p=0.004) were significantly more in triple negative breast cancer than non- triple negative breast cancer. In contrast, irregular shape (p=0.006) and spiculated margins (p=0.032) were significantly more in non-triple negative breast cancer. Old age (p=0.019), high histologic grade (p<0.0001), EGFR positivity (p<0.0001), p53 overexpression (p=0.038), and Ki 67 expression (<0.0001) were significantly associated with the triple negative breast cancer. Conclusion : MRI finding may be helpful for differentiation between triple negative and non-triple negative breast cancer.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.