Interobserver Variability of Ki-67 Measurement in Breast Cancer

정율리,장민혜,박소연,공경엽,정우희,이지신,The Korean Breast Pathology Ki-67 Study Group 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.2

Background: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Methods: Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. Results: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Conclusions: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.

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Intranasal Oxytocin Lessens the Attentional Bias to Adult Negative Faces: A Double Blind within-Subject Experiment

김율리,오승민,Freya Corfield,정다운,장은영,Janet Treasure 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.2

Objective Oxytocin is a neuropeptide that is involved in social emotional processing. A leading hypothesis is that oxytocin facilitates positive prosocial behaviors; the peptide may also play a more general role in inhibiting withdrawal-related social behaviors. The present study examined these possibilities. Methods A double-blind, placebo controlled crossover design was used with 31 healthy women. Forty-five minutes following the administration of 40 IU of intranasal oxytocin or a placebo, the participants were presented with two dot probe tests with pairs of face stimuli depicting emotional and neutral faces in adults. Results xytocin specifically reduced the attention bias toward the location of the faces of adults showing negative emotions, particularly in the case of disgust. Oxytocin did not enhance the attentional bias toward adult happy faces. The effect of oxytocin toward adult negative emotion was correlated with the sensitivity of the drive in the behavioral motivational system. Conclusion xytocin reduces attention to negative social emotions in adults, which supports oxytocin serves to inhibit withdrawal-related social behaviour.

Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value

우지원,정율리,안수민,강은영,김은규,김세현,김지현,김인아,박소연 한국유방암학회 2019 Journal of breast cancer Vol.22 No.3

Purpose: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. Methods: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. Results: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. Conclusion: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.

Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma

김길향,정율리,김보현,송보람,문경철 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.6

Background: Human epidermal growth factor receptor 2 (HER2) is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC) has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA) criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and compare their prognostic significance in UUTUC. Methods: HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC) using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+) and high (2+, 3+) groups. Results: Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001). The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004), but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161) in cancer-specific survival. Conclusions: HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

Benign Intraductal Papilloma without Atypia on Core Needle Biopsy Has a Low Rate of Upgrading to Malignancy after Excision

한송희,김미림,정율리,윤보라,장미정,김선미,강은영,김은규,박소연 한국유방암학회 2018 Journal of breast cancer Vol.21 No.1

Purpose: The management of benign intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial. This study was performed to evaluate the rate of upgrading to malignancy or high-risk lesions after excision and to identify factors associated with upgrading using a large series of benign IDP cases without atypia. Methods: We included patients who were diagnosed as having benign IDP without atypia on CNB and underwent surgical or vacuum-assisted excision between 2010 and 2015. We analyzed the clinical, radiologic, and histopathologic features of IDPs that were upgraded to malignancy or high-risk lesions after excision. Results: A total of 511 benign IDPs without atypia diagnosed via CNB were identified, of which 398 cases were treated with excision. After reviewing these cases, four cases of high-risk lesions in adjacent tissue on CNB, two cases which were revealed as papilloma with atypia, and nine cases of malignancy in the same breast were excluded. In the remaining 383 cases, the rate of upgrading to malignancy and high-risk lesions after excision was 0.8% and 4.4%, respectively. The presence of concurrent contralateral breast cancer, the presence of symptoms, and multifocality were factors significantly associated with upgrading to malignancy on subsequent excision. Surgical excision rather than vacuum-assisted excision was significantly associated with upgrading to high-risk lesions or malignancy. Conclusion: The rate of upgrading to malignancy for benign IDP without atypia was very low, suggesting that close clinical and radiologic observation may be sufficient for patients with benign IDP without atypia on CNB under proper settings.

Microinvasive Carcinoma versus Ductal Carcinoma In Situ: A Comparison of Clinicopathological Features and Clinical Outcomes

김미림,김현정,정율리,강은영,김은규,김세현,김유정,김지현,김인아,박소연 한국유방암학회 2018 Journal of breast cancer Vol.21 No.2

Purpose: Although microinvasive carcinoma is distinct from ductal carcinoma in situ (DCIS), the clinical significance of microinvasion in DCIS remains elusive. The purpose of this study is to evaluate the clinicopathological features and clinical outcomes of microinvasive carcinoma compared with pure DCIS. Methods: We assessed 613 cases of DCIS and microinvasive carcinoma that were consecutively resected from 2003 to 2014 and analyzed clinicopathological variables, expression of standard biomarkers such as the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), p53, and Ki-67, and tumor recurrence. Results: Among the 613 cases, 136 (22.2%) were classified as microinvasive carcinoma. Microinvasive carcinoma was significantly associated with DCIS with a large extent, high nuclear grade, necrosis, and comedotype architectural pattern. ER and PR expressions were dominantly observed in pure DCIS, whereas positive HER2 status, p53 overexpression, and high Ki-67 proliferation indices were more frequently observed in microinvasive carcinoma. Lymph node metastasis was found in only four cases of microinvasive carcinoma with multifocal microinvasion. In the multivariate analysis, DCIS with a large extent, comedo-type architectural pattern, and negative ER status were found to be independent predictors of microinvasion. During follow-up, 12 patients had ipsilateral breast recurrence, and no differences in recurrence rates were observed between patients with DCIS and those with microinvasive carcinoma. The triple-negative subtype was the only factor that was associated with tumor recurrence. Conclusion: Microinvasive carcinomas are distinct from DCIS in terms of clinicopathological features and biomarker expressions but are similar to DCIS in terms of clinical outcomes. Our results suggest that microinvasive carcinoma can be treated and followed up as pure DCIS.

MicroRNA-222 Expression as a Predictive Marker for Tumor Progression in Hormone Receptor-Positive Breast Cancer

한송희,김현정,곽재문,김미미,정율리,박소연 한국유방암학회 2017 Journal of breast cancer Vol.20 No.1

Purpose: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial- mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, Ncadherin, and E-cadherin) was evaluated using immunohistochemistry. Results: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR- 222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.

Relationship between Personality and Insomnia in Panic Disorder Patients

나혜란,강은호,유범희,우종민,김율리,이승환,김의정,이상열,정상근 대한신경정신의학회 2011 PSYCHIATRY INVESTIGATION Vol.8 No.2

Objective Panic disorder (PD) is frequently comorbid with insomnia, which could exacerbate panic symptoms and contribute to PD relapse. Research has suggested that characteristics are implicated in both PD and insomnia. However, there are no reports examining whether temperament and character affect insomnia in PD. Thus, we examined the relationship between insomnia and personality ch-aracteristics in PD patients. Methods Participants were 101 patients, recruited from 6 university hospitals in Korea, who met the DSM-IV-TR criteria for PD. We as-sessed sleep outcomes using the sleep items of 17-item Hamilton Depression Rating Scale (HAMD-17)(item 4=onset latency, item 5= middle awakening, and item 6=early awakening) and used the Cloninger’s Temperament and Character Inventory-Revised-Short to assess personality characteristics. To examine the relationship between personality and insomnia, we used analysis of variance with age, sex, and severity of depression (total HAMD scores minus sum of the three sleep items) as the covariates. Results There were no statistical differences (p>0.1) in demographic and clinical data between patients with and without insomnia. Initial insomnia (delayed sleep onset) correlated to a high score on the temperamental dimension of novelty seeking 3 (NS3)(F1,96=6.93, p=0.03). There were no statistical differences (p>0.1) in NS3 between patients with and without middle or terminal insomnia. Conclusion The present study suggests that higher NS3 is related to the development of initial insomnia in PD and that temperament and character should be considered when assessing sleep problems in PD patients.

Long-term Escitalopram Treatment in Korean Patients with Panic Disorder: A Prospective, Naturalistic, Open-label, Multicenter Trial

Kwan-Woo Choi,우종민,김율리,이승환,이상열,김의정,정상근,강은호,Jae-Hon Lee,유범희 대한정신약물학회 2012 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.10 No.1

Objective: Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. Methods: Clinical severity and functional impairment were assessed at baseline and at 4, 12, and 24 weeks after the treatment using the Panic Disorder Severity Scale and Sheehan Disability Scale. Ninety-six patients (80.7%) showed a treatment response,and 87 patients (73.1%) had attained remission after 24 weeks of escitalopram treatment. Results: Continuous improvement in the Panic Disorder Severity Scale and Sheehan Disability Scale scores was found over the 24 weeks of treatment. Conclusion: These findings suggest that escitalopram treatment is very effective for panic disorder in terms of both response and remission rates and that long-term pharmacotherapy with escitalopram continuously improved panic symptoms and functional disability in Korean patients with panic disorder.