PURPOSE: The purpose of this research is to elucidate the trend of incidence of childhood cancers for the recent 5 years and to use this study as a database of childhood cancers research by comparing to the existing data. METHODS: Childhood cancer patients registered in the cancer registry program of the Ministry of Health and Welfare in Korea during January 1, 1995 to December 31, 1999 were included as study samples. Our current data was obtained to be compared with the previous results 1st report during 1982~1987 and 2nd report during 1988~1992). Analysis of our study was obtained from the data of the patients of childhood cancers under 15 years old registered in the 128 hospitals, except for the patients who are registered repeatedly. RESULTS: Accumulated number of cases of the childhood cancers was 5, 433 (1.5% of the total cases of all ages). A male to female incidence ratio was 1.3 to 1. The most common malignant tumor was leukemia (33.1%). Out of 1, 800 cases of leukemia, 1, 142 cases (63.4%) were lymphoid leukemia, 468 cases (26.0%) were acute non-lymphocytic leukemia and 97 cases (5.4%) were chronic myeloid leukemia. The second most common malignancy was central nervous system tumor (16.0%), followed by lymphoma (8.0%), gonadal and germ cell tumors (7.9%), sympathetic nervous system tumor (6.7%), bone tumor (5.1%), soft tissue sarcoma (4.8%), renal tumor (4.0%), retinoblastoma (3.3%) and hepatic tumor (2.6%). The most common malignant tumor in the 0~4 year-old age was leukemia (32.6%), followed by central nervous system tumor (12.7%) and sympathetic nervous system tumor (11.5%). In the 5~9 year-old age group, the most common malignant tumor was leukemia (38.0%), as well, followed by central nervous system tumor (21.7%) and lymphoma (11.6%). In the 10~14 year-old age group, the most common cancers were leukemia (29.8%), central nervous system tumor (16.5%) and bone tumor (11.7%). CONCLUSION: We were unable to note any differences in the incidence of childhood cancers when comparing the current data and the previous ones.
Adolescent ; Central Nervous System ; Female ; Gonads ; Humans ; Incidence ; Korea* ; Leukemia ; Leukemia, Lymphoid ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal ; Retinoblastoma ; Sarcoma ; Sympathetic Nervous System

BACKGROUND: Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC. METHODS: In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression. RESULTS: No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups. CONCLUSIONS: High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.
Breast Neoplasms ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mutation, Missense ; Survival Rate ; Triple Negative Breast Neoplasms

BACKGROUND AND OBJECTIVES: Mechanism of inner ear hair cell distortion after noise exposure has been well described. The present study was designed to determine the response to the auditory system of a genetically well-defined laboratory mouse in preparation for examining the effect of noise on mice with specific genetic mutations. So it is important to recognize the relationship between noise exposure duration and hair cell morphological changes. We try to reveal the hearing loss and inner ear hair cell morphological changes after applying the noise protocol. SUBJECTS AND METHOD: The mice were BALB/c hybrids and aged 8 weeks. Six mice served as non-noise-exposed controls and 8 mice were exposed for 3 hours per day to white band noise with a center frequency from 0.2 kHz to 70 kHz and a sound pressure level of 120 dB. And we divided the noise exposure group into 3 subgroups(1 day, 3 day, 5 day noise exposure group). We checked the photographs of FITC phalloidin stain and scanning electron microscopy of cochlea after noise exposure. RESULTS: The hearing level of mice decreased after noise exposure. We could see the stereocilia damage in cochlea after FITC phalloidin stain in cochlea and sterocilia loss was more severe in basal turn. In scanning electron microscopy, morphological changes of stereocilia were observed to be more severe in the cochlear basal turn than other area. Significant hair cell loss in the cochlear basal turn could be calculated using cochleocytogram. CONCLUSION: 120dB broad white band noise can damage the hair cell of cochlea in mice. These changes were especially severe in the cochlear basal turn. Noise exposure duration is the other important factor in damaging cochlear hair cells. Therefore, we can guess that harmful noise level and noise exposure duration are the main risk factors that injure the inner ear hair cell.
Animals ; Cochlea ; Ear, Inner* ; Fluorescein-5-isothiocyanate ; Hair* ; Hearing ; Hearing Loss ; Mice* ; Microscopy, Electron, Scanning ; Noise* ; Phalloidine ; Risk Factors ; Stereocilia

OBJECTIVE: We wanted to evaluate the mammographic and sonographic differential features between pure (PT) and mixed tubular carcinoma (MT) of the breast. MATERIALS AND METHODS: Between January 1998 and May 2004, 17 PTs and 14 MTs were pathologically confirmed at our institution. The preoperative mammography (n = 26) and sonography (n = 28) were analyzed by three radiologists according to BI-RADS. RESULTS: On mammography, a mass was not detected in eight patients with PT and in one patient with MT (57% vs. 8%, respectively, p = 0.021), which was statistically different. The other findings on mammography and sonography showed no statistical differences between the PT and MT, although the numerical values were different. When the lesions were detected mammographically, an irregularly shaped mass with a spiculated margin was more frequently found in the MT than in the PT (100% vs. 83%, respectively, p = 0.353). On sonography, all 28 patients presented with a mass and most lesions showed as not being circumscribed, hypoechoic masses with an echogenic halo. Surrounding tissue changes and posterior shadowing were more frequently found in the MT than in the PT (75% vs. 50%, respectively, p = 0.253, 58% vs. 19%, respectively, p = 1.000). An oval shaped mass was more frequently found in the PT than in the MT (44% vs. 25%, respectively; p = 0.434). CONCLUSION: PT and MT cannot be precisely differentiated on mammography and sonography. However, the absence of a mass on mammography or the presence of an oval shaped mass would favor the diagnosis of PT. An irregularly shaped mass with surrounding tissue change and posterior shadowing on sonography would favor the diagnosis of MT and also a less favorable prognosis.
Adenocarcinoma/pathology/*radiography/*ultrasonography ; Adult ; Aged ; Breast Neoplasms/pathology/*radiography/*ultrasonography ; Diagnosis, Differential ; Female ; Humans ; Mammography ; Middle Aged ; Ultrasonography, Mammary

PURPOSE: The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. MATERIALS AND METHODS: A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). RESULTS: The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. CONCLUSION: MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.
Biomarkers ; Biopsy ; Cell Count ; Disease-Free Survival ; Drug Therapy ; Gene Expression ; Hematoxylin ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; Pathology ; Polymerase Chain Reaction ; Prognosis ; RNA, Messenger ; Triple Negative Breast Neoplasms* ; Venules*

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

PURPOSE: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. MATERIALS AND METHODS: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts. RESULTS: In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041). CONCLUSION: Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.
Antigen Presentation ; Breast Neoplasms* ; Breast* ; Cohort Studies ; Disease-Free Survival ; Endoplasmic Reticulum ; HLA Antigens ; HMGB1 Protein ; Humans ; Immune System ; Interferons ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating ; Neoplasm Metastasis ; Peptides ; Proteasome Endopeptidase Complex ; Triple Negative Breast Neoplasms

PURPOSE: Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing. METHODS: A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories. RESULTS: Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%. CONCLUSION: Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.
Breast ; Breast Neoplasms ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Quality Control ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Resin Cements

PURPOSE: For tumor growth, invasion and metastasis, a cascade of linked sequential biological events is essential; overproduction of growth factors, activation of proteolytic enzymes, induction of tumor angiogenesis, and enhanced tumor cell motility and attachment. We tried to test whether the biological therapy against the biological targets can modulate the specific biological characteristics, and furthermore increased anti-tumor effects can be induced when the biological therapy and cytotoxic chemotherapy were combined. MATERIALS AND METHODS: YCC-1, 2, 3, 7, and AGS human gastric cancer cell lines were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor (HBGF) inhibitor, Tranexamic acid as a plasmin inhibitor, Adriamycin as a chemotherapeutic agent, were selected. The methods were Northern blot analysis for the detection of Midkine (MK) expression, soft agar assay for autocrine tumorigenicity. The expression of uPA, PAI-1 was determined by ELISA, while the MMPs activities were evaluated by zymography. The effects of each drug on tumorigenicity and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively. RESULTS: YCC-3, 7, AGS cell lines expressed MK mRNA, whereas YCC-1, 2 did not. YCC-2 cell line showed increased expression of uPA and MMP activities. Only MK expressing YCC-3 and 7 cell lines showed the tumorigenicity. PPS suppressed the colony forming activities as much as Adriamycin did (PPS; 8~24%, Adriamycin; 12~40%), but it showed only cytostatic effects in cell proliferation assay (PPS; 60~103%, Adriamycin; 22~97%). When PPS was combined with Adriamycin on the Adriamycin resistant, MK expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that of PPS or Adriamycin single treatment was 40%, 22%, respectively (p=0.001). CONCLUSION: The modulation of specific biological targets can induce the anti-tumor effects. This suggests the possible clinical application of biological therapy in gastric cancer.
Agar ; Antifibrinolytic Agents ; Biological Therapy ; Blotting, Northern ; Cell Line* ; Cell Movement ; Cell Proliferation ; Doxorubicin ; Drug Therapy ; Enzyme-Linked Immunosorbent Assay ; Humans* ; Intercellular Signaling Peptides and Proteins ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Pentosan Sulfuric Polyester ; Peptide Hydrolases ; Plasminogen Activator Inhibitor 1 ; Population Characteristics ; RNA, Messenger ; Robenidine ; Stomach Neoplasms* ; Tranexamic Acid