High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Park, Heae Surng,Jang, Min Hye,Kim, Eun Joo,Kim, Hyun Jeong,Lee, Hee Jin,Kim, Yu Jung,Kim, Jee Hyun,Kang, Eunyoung,Kim, Sung-Won,Kim, In Ah,Park, So Yeon Springer Science and Business Media LLC 2014 Modern pathology Vol.27 No.9

<P>Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition, intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFR overexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases (33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4 of 151 cases (3%) and included G719A in exon 18 (n=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.</P>

18F-FDG PET/CT features of pulmonary sclerosing hemangioma.

Lee, Eugene,Park, Chang Min,Kang, Keon Wook,Goo, Jin Mo,Kim, Min A,Paeng, Jin Chul,Lee, Hyun Ju,Park, Heae Surng,Chung, Doo Hyun Acta Radiologica] 2013 Acta radiologica Vol.54 No.1

<P>Pulmonary sclerosing hemangioma (PSH) has been reported to show increased FDG uptake and be potential false-positives on 18F-FDG PET/CT examination. However, it is still unclear whether the previously-reported high FDG uptake is a universal characteristic of PSH, and furthermore, there have been no investigations on what kind of radiologic or histologic features may have been related with its FDG uptake values.</P>

Comparative analyses of overall survival in patients with anaplastic lymphoma kinase‐positive and matched wild‐type advanced nonsmall cell lung cancer

Lee, June Koo,Park, Heae Surng,Kim, Dong‐,Wan,Kulig, Kimary,Kim, Tae Min,Lee, Se‐,Hoon,Jeon, Yoon‐,Kyung,Chung, Doo Hyun,Heo, Dae Seog,Kim, Woo‐,Ho,Bang, Yung‐,Jue Wiley Subscription Services, Inc., A Wiley Company 2012 Cancer Vol.118 No.14

<P><B>Abstract</B></P><P><B>BACKGROUND:</B></P><P>The purpose of this study was to investigate the overall survival (OS) of patients with advanced <I>ALK</I>‐positive nonsmall cell lung cancer (NSCLC) who were managed in the pre‐ALK inhibitor era and to compare their survival with that of a matched case cohort of <I>ALK</I> wild‐type (WT) patients.</P><P><B>METHODS:</B></P><P>Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. <I>ALK</I> fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (<I>EGFR</I>) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) <I>ALK</I>‐positive patients, 2) <I>EGFR</I> mutation‐positive patients, and 3) <I>ALK</I>‐WT/<I>EGFR</I>‐WT patients. Progression‐free survival (PFS) after first‐line chemotherapy and EGFR TKIs also was analyzed.</P><P><B>RESULTS:</B></P><P>Twenty‐three patients were <I>ALK</I>‐positive according to FISH analysis and did not receive ALK inhibitors during follow‐up. The median OS for <I>ALK</I>‐positive patients, <I>EGFR</I> mutation‐positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs <I>EGFR</I> mutation‐positive patients, <I>P</I> = .001; vs WT/WT, <I>P</I> = .127). The PFS after first‐line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in <I>ALK</I>‐positive patients compared with the other 2 groups (vs <I>EGFR</I> mutation‐positive patients, <I>P</I> < .001; vs WT/WT, <I>P</I> < .021).</P><P><B>CONCLUSIONS:</B></P><P>In the pre‐ALK inhibitor era, <I>ALK</I>‐positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum‐based chemotherapy were not different from comparator groups, <I>ALK</I>‐positive patients were even more resistant to EGFR TKI treatment than WT/WT patients. Cancer 2012;3579–3586. © 2011 American Cancer Society.</P>

Correlation between the Size of the Solid Component on Thin-Section CT and the Invasive Component on Pathology in Small Lung Adenocarcinomas Manifesting as Ground-Glass Nodules

Lee, Kyung Hee,Goo, Jin Mo,Park, Sang Joon,Wi, Jae Yeon,Chung, Doo Hyun,Go, Heounjeong,Park, Heae Surng,Park, Chang Min,Lee, Sang Min Elsevier 2014 JOURNAL OF THORACIC ONCOLOGY Vol.9 No.1

Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis Associated With Mediastinal and Ovarian Teratomas: A Case Report

Lee Sue Hyun,Lee Chan Young,Park Heae Surng,Park Jin,윤지영 대한의학회 2023 Journal of Korean medical science Vol.38 No.6

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. Approximately 80% of patients with anti-NMDAR encephalitis are women. Tumors are detected in approximately 50% of female patients with anti-NMDAR encephalitis, of which 96% are ovarian teratomas. We describe the case of a 28-year-old woman diagnosed with anti-NMDAR encephalitis with mediastinal and bilateral ovarian teratomas in July 2019. The patient recovered following surgical management of the mediastinal mass and both ovarian teratomas, and immunotherapy. This case shows that teratomas can be found at multiple sites other than ovaries. Therefore, detecting teratomas using whole-body evaluation may be helpful for diagnosis and treatment.

Compound <i>EGFR</i> mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma

Kim, Eun Young,Cho, Eun Na,Park, Heae Surng,Hong, Ji Young,Lim, Seri,Youn, Jong Pil,Hwang, Seung Yong,Chang, Yoon Soo LANDES BIOSCIENCE 2016 Cancer Biology & Therapy Vol. No.

<P>Compound <I>EGFR</I> mutations, defined as double or multiple mutations in the <I>EGFR</I> tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of <I>EGFR</I> mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound <I>EGFR</I> mutations. Compound <I>EGFR</I> mutation was detected in 15 (24.6%) of 61 cases of <I>EGFR</I> mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 <I>vs</I>. 72.8 mo; <I>P</I> = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of <I>EGFR</I> mutations, including <I>ALK rearrangement</I>, <I>BCL2L11</I> intron 2 deletion, <I>KRAS</I> c.35G>A<I>, PIK3CA</I> c.1633G>A which are possible target of crizotinib, BH3 mimetics, <I>MEK</I> inhibitors, and <I>PI3K-tyrosine kinase inhibitors</I>, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (<I>P</I> = 0.001, independent sample <I>t</I>-test). Compound <I>EGFR</I> mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound <I>EGFR</I> mutations showed poor clinical outcomes, they should be closely monitored during follow-up.</P>

Tufting Enteropathy with EpCAM Mutations in Two Siblings

고재성,서정기,심정옥,Sol Ha Hwang,Heae Surng Park,강경훈 거트앤리버 소화기연관학회협의회 2010 Gut and Liver Vol.4 No.3

Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. The epithelial cell adhesion molecule gene (EpCAM) has recently been identified as the gene responsible for tufting enteropathy. Based on histology,a diagnosis of tufting enteropathy was made in two Korean siblings. They developed chronic diarrhea and failure to thrive. They had a broad nasal bridge and micrognathia. Duodenal and colonic biopsies showed villous atrophy, disorganization of surface enterocytes,and focal crowding resembling tufts. Protracted diarrhea continued and so cyclic parenteral nutrition was supplied. The sister had juvenile rheumatoid arthritis. Mutation analysis of EpCAM identified two compound heterozygous mutations in these siblings: 1) a donor splicing site mutation in intron 5 (c.491+1G>A) and 2) a novel nonsense mutation in exon 3 (c.316A>T,Lys106X). Analysis of EpCAM will be useful for genetic counseling and prenatal diagnosis of tufting enteropathy.

Metastatic cholangiocarcinoma as a cause of appendicitis

Sung Il Kang,Jeonghyun Kang,Heae Surng Park,Sung Ill Jang,Dong Ki Lee,Kang Young Lee,Seung-Kook Sohn 한국간담췌외과학회 2014 한국간담췌외과학회지 Vol.18 No.2

Metastatic carcinoma that causes appendicitis is extremely rare. To our knowledge, metastatic cholangiocarcinoma in the appendix has been reported in only 1 case in the English literature. We report herein the case of an 87-year-old woman who presented with abdominal pain and jaundice. Advanced cholangiocellular carcinoma and a proximal appendiceal mass with appendicitis were detected on contrast-enhanced computed tomography and positron emission tomography/computed tomography. After elective laparoscopic appendectomy and wedge resection of the cecum, pathologic results revealed metastatic adenocarcinoma from extrahepatic cholangiocellular carcinoma in the appendix.

정상 면역체계를 가진 청소년에서 발생한 종격동 림프절과 폐 크립토코쿠스증 1예

이지연 ( Jiyeon Lee ),조창민 ( Chang-min Cho ),조현혜 ( Hyun-hae Cho ),박혜성 ( Heae Surng Park ),김경효 ( Kyung-hyo Kim ) 대한소아감염학회 2021 Pediatric Infection and Vaccine Vol.28 No.2

Cryptococcus neoformans는 주로 면역이 저하된 환자에서 기회 감염을 일으키는 진균이다. 그러나 면역이 정상인 환자에서도 다양한 감염을 일으킬 수 있다. 림프절을 침범한 폐 크립토코쿠스증은 정상 면역을 가진 사람에서는 상대적으로 드물게 발생한다. 고열과 지속적인 기침을 주소로 병원에 온 17세 여자 청소년이 가슴X선 영상검사 및 컴퓨터단층촬영에서 전방 종격동에서 우측 쇄골하 부위까지 침범된 종괴를 보여 초음파 유도하 총생검 검사로 크립토코쿠스증을 진단하였다. 각종 면역 검사에서는 이상 소견이 발견되지 않았다. 환자는 2주간 암포테리신 B와 플루시토신으로 치료 후 8개월간 플루코나졸로 치료하였고 완쾌되었다. 본 증례를 통해 크립토코쿠스증의 특징을 이해하고 정상 면역 환자에게서도 크립토코쿠스증이 발생할 수 있음을 염두에 두고 진단을 내리는 것이 바람직하겠다. Cryptococcus neoformans is a fungus that primarily causes opportunistic infections in immunocompromised hosts. It can also cause various infections in immunocompetent patients. Pulmonary cryptococcosis involving the lymph node is relatively rare in immunocompetent patients. In this report, a previously healthy 17-year-old girl presented with high-grade fever and persistent cough. Chest X-ray and computed tomography (CT) scan revealed an anterior mediastinal conglomerate mass that expanded to the right supraclavicular area. Ultrasound-guided gun biopsy revealed histological evidence of cryptococcosis. Immunological screening tests did not identify immunodeficiency. She recovered completely with a combination therapy of amphotericin B and flucytosine for 2 weeks, followed by fluconazole for 8 months. The characteristics of cryptococcosis involving the mediastinal lymph node and the lung should be understood, and the possibility of cryptococcosis even in immunocompetent hosts should be considered.

Pulmonary Multinodular Epithelioid Hemangioendothelioma with Mixed Progression and Spontaneous Regression during a 7-Year Follow-Up: A Case Report and Review of Imaging Findings

Ga Young Yi,Yoo Kyung Kim,Kwan Chang Kim,Heae Surng Park 대한영상의학회 2022 대한영상의학회지 Vol.83 No.4

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of borderline or low-grade malignancy, and its prognosis is unpredictable. Herein, we describe the case of a 47-year-old asymptomatic female with a diagnosis of multinodular PEH. During a 7-year followup, the nodules with large size and high 18F-fluorodeoxyglucose uptake in the initial study showed progression with increasing sizes; however, most small nodules (size < 1 cm) demonstrated spontaneous regression with peripheral rim or nodular calcification. The patient underwent surgical resection for an enlarged nodule. Of note, it is unusual for an individual to have mixed progression and regression concomitantly, which may be helpful in predicting the prognosis.