دورية أكاديمية
أعرض في EDS

Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poor survival.

التفاصيل البيبلوغرافية
العنوان: Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poor survival.
المؤلفون: Kloth JN; Department of Pathology, The Leiden University Medical Center, Leiden, The Netherlands., Kenter GG, Spijker HS, Uljee S, Corver WE, Jordanova ES, Fleuren GJ, Gorter A
المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2008 Jul; Vol. 21 (7), pp. 866-75. Date of Electronic Publication: 2008 Apr 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2023- : [New York] : Elsevier Inc.
Original Publication: Baltimore, MD : Williams & Wilkins, c1988-
مواضيع طبية MeSH: Biomarkers, Tumor/*metabolism , Carcinoma, Squamous Cell/*metabolism , Cell Nucleus/*metabolism , Smad2 Protein/*metabolism , Smad4 Protein/*metabolism , Uterine Cervical Neoplasms/*metabolism, Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology ; Cell Nucleus/pathology ; DNA Methylation ; DNA Mutational Analysis ; DNA, Neoplasm/analysis ; Female ; Gene Silencing ; Humans ; Hysterectomy ; Loss of Heterozygosity ; Netherlands/epidemiology ; Prognosis ; Smad2 Protein/genetics ; Smad4 Protein/genetics ; Survival Rate ; Tissue Array Analysis ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/mortality ; Uterine Cervical Neoplasms/pathology
مستخلص: Alterations in transforming growth factor-beta signaling, due to a decrease in Smad2 and especially Smad4 expression, has primarily been reported in pancreatic and colorectal cancers, although loss of the chromosomal region 18q21.1, containing the loci of Smad2 and Smad4, is among the most frequent molecular alterations in cervical cancer. The aim of our study was to investigate whether decreased Smad2 and Smad4 protein expression in primary cervical cancers is associated with molecular alterations at 18q21.1, mutations in the functional domains of Smad2 and Smad4 or hypermethylation, and to assess the biological relevance of decreased Smad2 and Smad4 expression. Subsequently, Smad2, Smad4 and p21 protein expression was determined by immunohistochemistry in 117 primary cervical carcinomas, assembled in a tissue array. Smad signaling was shown to be associated with p21 mRNA expression. All the tumors expressed Smad2 or Smad4. Weak cytoplasmic Smad2 or weak cytoplasmic Smad4 expression could not be attributed to loss of heterozygosity at 18q21.1. Despite weak/moderate Smad2 expression and absent nuclear Smad4 expression, the coding regions of the functional MH1 and MH2 domains of Smad2 and Smad4 were unchanged, as assessed by sequence analysis. The Smad4 promoter region was unmethylated in tumor samples with weak/moderate cytoplasmic Smad4 expression. Remarkably, both weak cytoplasmic Smad4 expression and absent nuclear Smad4 expression significantly correlated with poor disease-free (P=0.003 and P=0.003, respectively) and overall 5-year survival (P=0.003 and P=0.010, respectively). Our findings support the hypothesis that Smad4 is a target molecule for functional inactivation in cervical cancer.
المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (DNA, Neoplasm)
0 (SMAD2 protein, human)
0 (SMAD4 protein, human)
0 (Smad2 Protein)
0 (Smad4 Protein)
تواريخ الأحداث: Date Created: 20080422 Date Completed: 20080930 Latest Revision: 20230210
رمز التحديث: 20231215
DOI: 10.1038/modpathol.2008.62
PMID: 18425078
قاعدة البيانات: MEDLINE
الوصف
تدمد:1530-0285
DOI:10.1038/modpathol.2008.62