Differential Expression of CXCR4 in Conventional High-grade and Low-grade Central Osteosarcoma and Its Prognostic Implications

박혜림,서진원,박용구,Park, Hye-Rim,Seo, Jin-Won,Bacchini, Patrizia,Bertoni, Franco,Park, Yong-Koo The Korean Musculoskeletal Tumor Society 2012 대한골관절종양학회지 Vol.18 No.1

목적: 케모카인 수용체인 CXCR4는 암에서 발현되며 암의 전이에 관여한다고 알려져 있다. 저자들은 통상적인 조직학적으로 고등급인 골육종과 저등급 중심부 골육종에서 CXCR4 발현을 비교하고 CXCR4 발현과 예후 간에 연관성이 있는지 살펴보았다. 대상 및 방법: 총 63명의 골육종 환자에서 CXCR4에 대한 면역조직화학검사를 시행하였고 임상적, 병리학적 인자 및 전체적인 생존율과의 연관성을 살펴보았다. 결과: CXCR4는 통상적인 고등급(조직학적 등급 3 및 4) 골육종의 76.3%에서 발현된 반면 저등급(조직학적 등급 1 및 2) 중심부 골육종의 36%에서 발현되었다. 또한 고등급 골육종의 47.4%에서 미만성으로 발현된 반면 모든 저등급 골육종은 병소에 국한되어 발현되었다. CXCR4 발현은 조직학적 등급과 통계학적으로 유의한 상관관계를 나타내었다(p<0.0001). 전체적인 생존률은 CXCR4 발현 증가(p=0.0058), 고등급의 조직학적 등급(p<0.0001), 어린 연령(p=0.0140)에 따라 유의하게 감소하였지만, 성별, 종양 크기, AJCC 병기와는 연관성이 뚜렷하지 않았다. 결론: CXCR4 발현은 골육종에서 고도의 조직학적 분화도가 나쁜 등급 및 불량한 예후와 연관된다. Purpose: The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancer and has been shown to participate in cancer metastasis. We compared the expression of CXCR4 in conventional high-grade and low-grade central osteosarcomas, and determined if an association between CXCR4 expression and prognosis could be made. Materials and Methods: We performed the immunohistochemistry for CXCR4 in a total of 63 patients with osteosarcoma and determined the relationships according to the clinicopathologic variables and overall survival rates. Results: CXCR4 was detected in 76.3% of conventional high-grade osteosarcoma patients and in 36% of low-grade central osteosarcomas. Diffuse expression was noted in 47.4% of the high-grade osteosarcomas and all low-grade cases were focal positive. CXCR4 expression was significantly correlated with histologic grade (p<0.0001). While overall survival rate was reduced significantly with increased CXCR4 expression (p=0.0058), higher histologic grade (p<0.0001), and younger age (p=0.0140), survival rate did not correlate with gender, tumor size, or AJCC stage. Conclusion: Our results suggest that CXCR4 expression is associated with higher-grade tumors and with poor prognosis for osteosarcoma patients.

자궁 경부의 선암과 혼합된 신경내분비 소세포 암종 - 1 증례 보고 -

박혜림,이용우,박영의,Park, Hye-Rim,Lee, Yong-Woo,Park, Young-Euy 대한세포병리학회 1990 대한세포병리학회지 Vol.1 No.1

Small cell neuroendocrine carcinoma of the uterine cervix is a distinct subtype of cervical cancer that appears analogous to oat cell carcinoma and carcinoid tumors of the lung. It has been assumed to be derived from the neural crest via argyrophilic cells in the normal endocervix. We have recently encountered a case of small cell neuroendocrine carcinoma of the uterine cervix coexisting with adenocarcinoma which was argyrophil negative. A 66-year-old multiparous woman was admitted because of vaginal bleeding for 2 months. Cervicovaginal smear revealed several scattered clusters and sheets of monotonous small cells with some peripheral palisading in the background of hemorrhage and necrosis. Radical hysterectomy specimen revealed an ulcerofungating tumor on endocervical canal which was composed of two components. Major component of the tumor was made up of monomorphic population of small oval-shaped tumor cells arranged in sheets and partly in acinar structures or trabecular fashion. Other component was adenocarcinoma, endocervical well-differentiated type. Argyrophilia was present on the Grimelius stain and immunohistochemical studies revealed diffuse positivity to neuron-specific enolase and carcinoembryonic antigen. Electron microscopic examination showed clusters of small round to oval cells, which had a few well-formed desmosomes and several membrane-bound, dense-core neurosectetory granules.

전립선 선암의 화상 계측에 관한 연구

박혜림,채승완,손진희,박영의,Park, Hye-Rim,Chae, Seung-Wan,Sohn, Jin-Hee,Park, Young-Euy 대한세포병리학회 1995 대한세포병리학회지 Vol.6 No.2

Morphometry of nuclei of the benign and malignant prostatic lesions was performed to study the relationship between nuclear size and shape and the prognosis of prostatic adenocarcinoma fifty one cases of prostatic adenocarcinoma and 13 cases of benign prostatic hyperplasia were included to evaluate area, perimeter, Dmax, Dmin, and 5 form factors of the nuclei by image analyzer(Zeiss Ibas 2000) using hematoxylin-eosin stained slides. All analytic factors of nuclear size and shape were significantly different between benign lesions and adenocarcinomas. Increased nuclear size was associated with nuclear irregularity, presence of metastasis, advanced clinical stage, and high Gleason's grade and score of prostatic adenocarcinoma. On Kaplan-Meier method, survival was decreased with older age, no hormonal treatment, stage D, high Gleason's grade and stage as well as with larger size and irregular shape of the nuclei in conclusion, morphometry of nuclei of the prostate can be a helpful tool to differentiate between be nign and malignant lesions. Nuclear morphology is thought to be associated with prognosis of prostatic adenocarcinoma.

대퇴골에 발생한 역분화성 방골성 골육종 - 증례보고 -

박혜림,박용구,장준동,남은숙,손진희,Park, Hye-Rim,Park, Yong-Koo,Jang, Joon-Dong,Nam, Eun-Sook,Sohn, Jin-Hee The Korean Musculoskeletal Tumor Society 1999 대한골관절종양학회지 Vol.5 No.1

We present a case of parosteal osteosarcoma of the femur with secondary dedifferentiation. This 57-year-old woman was radiologically diagnosed as a parosteal osteosarcoma in 1987. In 1992, excisional biopsy revealed a classical parosteal osteosarcoma with diploidy DNA pattern. In 1998, she revisited due to a recurrent tumor with pathologic fracture. The resected specimen showed a classic parosteal osteosarcoma with area of dedifferentiation, showing high-grade spindle cell sarcoma. This dedifferentiated area revealed aneuploidy cell population on DNA flow cytometry. This case reminds us that not all parosteal osteosarcomas are low-grade lesions. Some low-grade lesions may dedifferentiate to become high-grade tumors after inadequate excision. 57세 여자 환자의 대퇴골 원위부에 발생한 방골성 골육종이 이차적 역분화를 일으킨 예를 치험하여 이를 보고하고자 한다. 57세 여자 환자가 1987년 방사선 소견상 대퇴골 방골성 골육종으로 진단되었고, 1992년 절제 생검을 시행한 결과 통상적인 방골성 골육종이었고, 이배수성의 DNA를 나타내었다. 1998년 환자는 병적 골절이 동반된 재발성 종양으로 재입원 하였다. 절제된 종양은 통상적인 방골성 골육종의 부위뿐만 아니라, 고등급의 방추성 세포 육종의 특정을 보이는 역분화 부위가 흔재하여 있었다. 이러한 역분화 부위는 유세포 측정을 이용한 DNA 검사상 이수배수성을 나타내었다. 본 증례를 통하여 모든 방골성 골육종이 저등급 병변은 아니고, 일부의 저등급 병변이 불충분한 절제 후에 고등급의 종양으로 역분화할 수 있음을 알 수 있다.

Profiling of miRNA expression in mice kidney with diabetic nephropathy

박혜림,Seung Eun Lee,김혜미,Seeun Jeon,Dongkyo Han,Young-Ho Jin,조정제,안현종,Cheung-Seog Park,Jongsung Lee,Yong Seek Park 대한독성 유전단백체 학회 2018 Molecular & cellular toxicology Vol.14 No.4

Backgrounds: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM) and the worldwide prevalence of DN has continued to increase. DN causes cellular stress and inflammation, which induces death of renal cells and dysfunction of blood vessels. MicroRNAs (miRNAs) are small interfering RNAs that negatively regulate mRNA gene expression. Various human diseases are attributed to aberrant miRNAs expression, and miRNAs levels are used as markers for diagnosis and classification of diseases. However, the profile of miRNAs in DN mouse have not been fully explained, we analyzed miRNAs expression in the kidney of diabetic mice. Methods: C57BL6 male mice were injected with streptozotocin (50 mg/kg body weight) for five consecutive days to induce DM. Mice were sacrificed after 16 weeks and RNAs were extracted from the kidneys and analyzed via microarray profiling. Results: Our results confirmed that 137 miRNAs expression was altered in DM. These miRNAs showed pairwise correlations with 48 mRNAs in DM kidney. Furthermore, Differential expressed miRNAs were characterized by Gene Ontology (GO) enrichment analysis and signaling pathway using DAVID. Conclusion: Our findings may provide that changes in miRNA expression in mice with diabetic nephropathy influences disease progression and might provide insights into the molecular mechanisms underlying DN.

Profiling of gene expression using microarray in acroleintreated human pulmonary fibroblasts

박혜림,Seung Eun Lee,Gun Woo Son,Hong Duck Yun,Cheung-Seog Park,안현종,조정제,Jongsung Lee,Yong Seek Park,J.Lee 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.1

Pulmonary fibroblasts are essential for the integrity of alveolar structures and to restore lung tissue after injury. They are also important for inflammatory responses through their ability to attract leukocytes. Cigarette smoke has many harmful components, and causes various pulmonary and lung diseases including chronic obstructive pulmonary disease (COPD), chronic bronchitis, and emphysema. Acrolein (ACR), one of the compounds in cigarette smoke, induces inflammatory cytokines and the generation of DNA adducts, resulting in dysfunction of respiratory cells such as pulmonary fibroblasts. In this study, we examined the expression of genes in ACR-treated human pulmonary fibroblasts by microarray profiling. We identified 2,378 and 312 genes that were differentially expressed within 6 h of treatment with 10 μM or 25 μM ACR, respectively. These genes were classified as being involved in many biological processes including apoptosis, immune responses, cell cycle, and signal transduction. Some genes, including HSPA1B, HMOX1, CASP3, PRDX3, and ANXA1, are related to COPD. These results support the hypothesis that ACR may increase cytotoxicity and tissue injury in respiratory cells and may attribute to the development of pulmonary disease.

STAT3 is Activated in a Subset of Benign and Malignant Chondroid Tumors

박혜림,박용구,Park, Hye-Rim,Park, Yong-Koo The Korean Musculoskeletal Tumor Society 2009 대한골관절종양학회지 Vol.15 No.2

목적: STAT3는 주요 세포 진행과정을 조절하는 암유전자로, 활성화되면 여러 악성종양의 생물학적, 임상적 특징과 연관된다고 알려져 있고, 한편 배아줄기세포와 연관된 유전자이기도 하다. 본 연구에서는 연골종양의 발생에 STAT3 활성화가 관여하는지 살펴보았다. 대상 및 방법: 총 33예의 각종 양성 및 악성 연골종양에서 STAT3 활성화를 살펴보기 위해 활성화된 $pSTAT3^{tyr705}$에 특이한 단클론성 항체를 이용한 면역조직화학법을 시행하였다. 결과: 통상적인 연골육종 17예 중, 조직학적 등급 3의 연골육종은 3예(50%)에서 pSTAT3에 양성이었고, 등급 1 및 2 연골육종은 모두 음성이었다. 즉 pSTAT3 양성도는 조직학적 등급과 통계학적으로 유의한 상관관계(p=0.0432)를 나타내었다. 또한 투명세포 연골육종 2예(50%)도 pSTAT3에 양성이었다. 내연골종, 연골모세포종, 연골점액양섬유종 등 12예의 양성 연골종양 중 6예(50%)에서 pSTAT3가 관찰되었다. 결론: STAT3 활성화는 통상적인 연골육종 중 고도의 조직학적 분화도가 나쁜 등급에서 주로 발견된다. 배아줄기세포 표지자인 STAT3가 양성 및 악성 연골종양 일부에서 활성화되는 것으로 미루어보아 연골 기원 종양에서도 악성종양의 줄기세포 가설을 제안할 수 있다. Purpose: STAT3 is an oncogene that regulates critical cellular processes, and its constitutive activation has been demonstrated to correlate with biological and clinical features in many types of human malignancy. Materials and Methods: In this study, STAT3 activation was assessed in variable benign and malignant chondroid tumors in bone by immunohistochemistry using a monoclonal antibody specific for $tyrosine^{705}$-phosphorylated STAT3 ($pSTAT3^{tyr705}$). Results: Among conventional chondrosarcomas (n=17), three cases(50%) of grade III chondrosarcomas were pSTAT3-positive. All grade I and II chondrosarcomas were pSTAT3-negative. This pSTAT3 positivity according to the histologic grade was statistically significant (p=0.0432). Two cases(50%) of clear cell chondrosarcomas were pSTAT3-positive. Six cases (50%) among 12 benign chondroid tumors(6 enchondromas, 3 chondroblastomas, and 3 chondromyxoid fibromas) were also $pSTAT3^{tyr705}$-positive. Conclusion: In conclusion, STAT3 activation is associated with higher tumor grade in conventional chondrosarcomas. Our results suggest that STAT3 is activated in a subset of benign and malignant chondroid tumors, and may support the extension of the cancer stem cell hypothesis to include tumors of cartilaginous lineage.

단순포진 Virus 감염의 세포학적 진단시 면역조직 화학법의 적용

박혜림,이갑노,백승룡,Park, Hye-Rim,Lee, Kap-No,Paik, Seung-Yong 대한세포병리학회 1990 대한세포병리학회지 Vol.1 No.1

Herpes simplex virus type 1 and 2(HSV-1, HSV-2) are the ubiquitous human pathogens responsible for a variety of afflictions. HSV-2 is one of the viruses that were suspected of promoting carcinogenesis in the uterine cervix. Certainly, there is a need for the more sensitive and accurate laboratory techniques for HSV detection. We examined total 80 cases of smears including 17 Tzanck smears of skin and 63 cases of Papanicolaou smears from total 77 patients with clinical impression of herpetic infections, from September, 1985 through August, 1989. Immunohistochemical typings for HSV-1 and HSV-2 were performed together with routine cytologic findings and compared. The results are as follows : 1) Patients were 9 males and 33 females, and age distribution was between 5 and 71 years. 2) Subjective symptoms such as ulceration, vesicle, vaginal discharge, pruritus, and pain were complained in 36 patients and 38 cases were genital herpes. Recurrence was noted in 11 cases. 3) Positive results were obtained in 42 among 80 cases. 4) Both routine cytology and immunohistochemical staining were positive in 13 cases and in 24 cases only immunohistochemical staining were positive. 5 cases were positive only in routine cytologic smears. 5) The cases that immunocytochemical stain had been performed were 37 cases, which were all positive in type 2. Among the above 37 cases, type 1 also were positive in 5 cases. The results show that the immunoperoxidase technique is one of the rapid and reliable method to confirm the herpetic infection when suspected and that it is particularly useful when the Papanicolaou smear findings are equivocal.

Cyclooxygenase-2 Expression in Benign and Malignant Chondroid Tumors

박혜림,민광선,박용구,Park, Hye-Rim,Min, Kwang-Seon,Park, Yong-Koo The Korean Musculoskeletal Tumor Society 2007 대한골관절종양학회지 Vol.13 No.2

목적: 최근 골 및 연부조직 종양을 포함한 각종 악성 종양에서 cyclooxygenase-2 (COX-2) 의 발현 증가가 보고되고 있다. 그러나 연골 종양에서의 COX-2 발현에 대해서는 별로 알려진 바가 없다. 대상 및 방법: 내연골종 10예, 연골모세포종 11예, 연골점액양섬유종 5예, 통상적 연골육종 17예, 투명세포 연골육종 7예, 간엽성 연골육종 6예를 대상으로 COX-2에 대한 면역조직화학법을 시행하였다. 결과: 양성 연골 종양 중 연골모세포종 11예 중 6예(54.5%)에서 특징적인 강한 양성 반응을 나타내었다. 내연골종과 연골점액양섬유종은 단 1예를 제외하고는 모든 증례에서 음성이었다. 통상적인 연골육종에서 3예(17.6%)는 COX-2에 대해 강한 양성 반응을 보였는데 이러한 양성 증례는 모두 조직학적 등급 3의 분화가 나쁜 연골육종이었다. 투명세포 연골육종 중 2예(28.5%)는 국소적인 양성 반응을 나타내었고 모든 간엽성 연골육종은 음성이었다. 결론: 이러한 결과는 통상적인 연골육종에서 COX-2 과발현이 조직학적 등급 진행과 관계된 소견임을 시사한다. 연골모세포종의 COX-2 발현은 특별히 이 종양에 동반되는 종양 주변부의 염증성 변화를 유발하는 중요한 요소로 생각된다. Purpose: Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in various human malignancies to include various bone and soft tissue tumors. However, little is known with regard to COX-2 expression patterns in chondroid tumors. Materials and Methods: Immunohistochemistry assays were performed for COX-2 in enchondromas (n=10), chondroblastomas (n=11), chondromyxoid fibromas (n=5), conventional chondrosarcomas (n=17), clear cell chondrosarcomas (n=7), and mesenchymal chondrosarcomas (n=6). Results: Among the benign chondroid tumors, chondroblastomas revealed characteristic strong positivity in 6 of 11 cases(54.5%). All enchondromas and chondromyxoid fibromas were negative except in one case. In conventional chondrosarcomas, three cases(17.6%) were strongly reactive with COX-2 and all positive cases represented grade III chondrosarcomas. Clear cell chondrosarcomas were found to be focally positive in two cases(28.5%), while all mesenchymal chondrosarcomas were negative. Conclusions: These findings suggest that COX-2 overexpression in conventional chondrosarcoma may represent an advanced histologic grade. Interestingly, expression of COX-2 in chondroblastomas could be an important factor for inducing peritumoral inflammatory changes in these specific tumors.

Giant Cell Tumor of the Rib: Two Cases of F-18 FDG PET/CT Findings

박혜림,유이령,이영주,Sonya Youngju Park,정찬권 대한핵의학회 2017 핵의학 분자영상 Vol.51 No.2

We report two cases of giant cell tumor arising fromthe rib and their F-18 FDG PET/CT findings. The two patientscomplained of chest wall pain, and large lobulated soft tissuemasses with intense FDG uptake were seen on F-18 FDGPET/CT. A malignant tumor such as osteosarcoma orchondrosarcoma was suspected due to the large size of themass, bony destruction, and intense FDG uptake. En blocresection was performed and final pathologic results revealedgiant cell tumor of the rib. Giant cell tumor of the rib is veryrare, and larger lesions with high FDG uptake can bemisdiagnosed as an intrathoracic malignancy arising fromthe rib, pleura, or chest wall.