Sinonasal lymphomas comprise NK/T-cell (NKTCL) type and B-cell type with unique geographical development. In this study, mutations of p53, K-ras, c-kit, ß-catenin, and bak gene were analyzed using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) followed by direct sequencing in 41 sinonasal lymphomas (27 NKTCL and 14 B-cell type) from Indonesia. In situ hybridization study with EBER-1 probe revealed that 85% of NKTCL cases were EBV positive, but none of B-cell type was EBV positive. Frequency of mutations in p53, K-ras, c-kit, ß-catenin, and bak gene was 62.9%, 0%, 11.1%, 18.5%, and 25.9%, respectively, in NKTCL, and 71.4%, 0%, 23.1%, 21.4%, and 57.1%, respectively, in B-cell cases, showing that mutation frequency in all genes was higher in B-cell than in NKTCL cases. These findings suggest that gene mutations might be the driving-force for B-cell lymphoma, whereas combined EBV infection and gene mutations contribute to NKTCL development in Indonesia.
AbstrakLimfoma sinonasal merupakan kelainan yang jarang dijumpai yang mencakup jenis sel NK/T atau sel B. Penelitian2 terdahulu menunjukkan adanya perbedaan angka kejadian limfoma NK/T (LNKT) yang sesuai daerah geografis serta kaitan yang sangat tinggi dengan infeksi virus Epstein Barr. Penelitian yang dilakukan terhadap 4l kasus penyakit limfoproliferatif sinonasal yang tersimpan di arsip Bagian Patologi Anatomik Fakultas Kedokteran Universitas Indonesia dalam kurun waktu 1994-2002 menunjukkan 35 kasus merupakan limfoma sinonasal. Pulasan imunohistokimia membuktikan 20 kasus (57%) sebagai LNKT dan 15 kasus (43%) limfoma sel B jenis sel besar. LNKT menunjukkan laki2 lebih banyak dari wanita (L:W=4:1) serta usia yng lebih muda (median 37 tahun); sedangkan limfoma sel B lebih banyak pada wanita (1:1.5) serta usia yang lebih tua (median 49 tahun). Hasil pemeriksaan genom virus Epstein Barr dengan cara hibridisasi in situ menggunakan pelacak EBER-1 menunjukkan 90% LNKT positif dan negatif pada semua limfoma sel B. Tulisan ini merupakan laporan limfoma sinonasal yang pertama dari Indonesia yang menunjukkan predominasi relatif limfoma sel B dibandingkan dengan beberapa negara Asia lainnya. Tidak adanya kaitan dengan virus Epstein Barr pada limfoma sel B juga berbeda dengan penemuan di negara Asia lain (positivitas 25-4l%) . Predominasi limfoma sel B tanpa kaitan dengan virus Epstein Barr mengarah pada kemungkinan adanya faktor etiologik yang spesifik untuk Indonesia. Abstract Sinonasal lymphoma is a rare disease with NK/T-cell (NKTC) or B-cell immunophenotype. Previous study revealed the geographic difference in frequency of NKTC lymphoma (NKTCL) and almost constant association with Epstein-Barr virus (EBV) infection.Through review of 41 cases with sinonasal lymphoproliferative diseases registered in the Department of Anatomical Pathology, University of Indonesia during the period 1994 to 2002, thirty-five were accepted as sinonasal lymphoma. Immunohistochemistry revealed that 20 cases (57%) were NK/T-cell type and 15 (43%) B-cell type with large cell morphology, i.e.,diffuse large B-cell lymphoma. NKTCL showed a marked male preponderance (M/F= 4:1) and younger onset of disease (median age, 37 years), and Bcell lymphoma showed a relative female preponderance (1:1.5) and older disease onset (median age, 49 years). In situ hybridization using EBER-1 probe revealed that 90 % of NKTCL were EBV-positive, but none of B-cell lymphoma were EBV-positive. This is the first report on sinonasal lymphoma in Indonesia showing relative predominance of B-cell lymphoma compared to other Asian countries and Peru (14-24 %). Lack of EBV-association in Indonesian sinonasal B-cell lymphoma showed a marked contrast to that in other Asian countries (EBV positive rate,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Predominance of sinonasal B-cell lymphoma without EBV genome might suggest presence of specific etiologic factors in Indonesia. (Med J Indones 2004; 13: 71-6)
Penelitian cara kasus-kontrol telah dilakukan untuk analisafaktor risiko pada kanker payudara wanita Indonesia. Tiga ratus kasus dan 600 kontrol diwawancara menggunakan kuesioner baku untuk pengumpulan data epidemiologik. Subyek diteliti untuk berbagai data demografik, status reproduksi, perilaku seks, kebiasaan makan dan cara-cara hidup lain. Data dianalisa untuk menentukan faktor risiko yang bermakna menggunakan analisa univariat dan multivariat. Perhatian khusus diberikan untuk evaluasi faktor risiko berkaitan dengan golongan etnik yang berbeda. Suku Sunda, yang dikenal berbeda dengan suku-suku lain dalam hal kebiasaan makan dan cara hidup yang lebih tradisional, dibandingkan dangan suku-sulw non-Sunda. Hasilnya menampakkan bahwa faktor-faktor risiko berikut: ting kat sosial ekonomi dan pendidikan, tempat tinggal (pedesaan versus perkotaan), status perkawinan dan pekerjaan tidak bermakna, sedangkan di antara suku non-Sunda, menstruasi yang tidak teratur dan trauma payudara meningkatkan risiko, dengan OR dan C/95% masing-masing
Abstrak AbstractBackground: Basal-like breast cancer is difficult to treat with standard regimen therapy, because it doesn't express hormone receptors or epidermal growth factor receptors. Identification of oncogenesis pathway is expected to find molecules which can be used as target for therapy. One candidate molecule is topoisomerase-IIα whose expression is regulated by p53. This study aimed to compare the expression of mutant p53 proteins and topoisomerase IIα in basal-like and non basal-like breast cancer, and to determine the association between mutant p53 proteins and topoisomerase IIα in basal-like group. Methods:The samples were 40 formalin fixed paraffin embedded tissues from verified triple negative breast cancer tissue. The samples were divided into 2 groups, basal-like and non basal-like breast cancer, based on cytokeratin -5 (CK-5) expression. Mutant p53 proteins and topoisomerase IIα were stained using immunohistochemistry method, scored and compared. Statistical test used SPSS software version 16 for descriptive statistics, kappa test, normality test, comparison of two mean, and categorical comparison.Results: Median (min-max) of mutant p53 protein expression in basal-like group was 21 (0-100), the non basal-like group was 2 (0-80), p = 0.061. Min-max of topoisomerase IIα in basal-like group was 263 (15-492), non basal-like group was 262 (0-481), p = 0.409. There was an association between mutant p53 positivity with breast cancer subtype (p = 0.027) and between mutant p53-topoisomerase IIα coexpression with breast cancer subtype (p = 0.018). Conclusion:Co-expression of mutant p53 with topoisomerase IIα has the role in one of the pathway of basal-like breast cancer pathogenesis.
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