ABSTRACT
Inhibitor of differentiation/DNA binding (Id) proteins are transcription factors, involved in cell cycle regulation and neoangiogenesis. Using immunohistochemistry, we investigated the prognostic influence of Id-1, Id-2, and Id-3 expression in 89 patients with cervical cancer stage pT(1b). In univariate and multivariate analysis, patients with strong or moderate expression of Id-1 had a significant shorter overall survival time (P = 0.0144, log-rank test) and disease-free survival time (P = 0.0107, log-rank test) compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.
Subject(s)
Biomarkers, Tumor/biosynthesis , DNA-Binding Proteins/biosynthesis , Neoplasm Proteins , Repressor Proteins , Transcription Factors/biosynthesis , Uterine Cervical Neoplasms/metabolism , Biomarkers, Tumor/physiology , DNA-Binding Proteins/physiology , Female , Humans , Immunohistochemistry , Inhibitor of Differentiation Protein 1 , Inhibitor of Differentiation Protein 2 , Inhibitor of Differentiation Proteins , Microcirculation , Multivariate Analysis , Neoplasm Staging , Neovascularization, Pathologic/metabolism , Prognosis , Survival Rate , Transcription Factors/physiology , Uterine Cervical Neoplasms/blood supply , Uterine Cervical Neoplasms/pathologyABSTRACT
Downregulation of KAI1 metastasis suppressor protein is associated with dismal prognosis in a variety of cancers. Mutation of p53 was suggested to be involved in KAI1-downregulation. In cervical cancer, p53 is inactivated by human papillomavirus (HPV) oncoprotein E6 with the grade of inactivation depending on the HPV type. KAI1-expression was immunohistochemically determined in 67 specimens of cervical cancer, HPV-typing was performed using polymerase chain reaction (PCR), cloning, and sequencing. KAI1-downregulation was found in 68.1% of patients, HPV-infection in 91%. There was no association of KAI1-downregulation and infection with a particular HPV type. KAI1-downregulation in cervical cancer seems independent of HPV-E6 induced p53 inactivation.
Subject(s)
Antigens, CD/biosynthesis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , Membrane Glycoproteins/biosynthesis , Papillomaviridae , Papillomavirus Infections/metabolism , Proto-Oncogene Proteins , Tumor Virus Infections/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/virology , Antigens, CD/genetics , Carcinoma, Squamous Cell/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kangai-1 Protein , Membrane Glycoproteins/genetics , Middle Aged , Papillomaviridae/classification , Papillomavirus Infections/virology , Tumor Virus Infections/virology , Uterine Cervical Neoplasms/geneticsABSTRACT
BACKGROUND: In early-stage cervical cancer, high lymphatic microvessel density (LMVD) indicates favorable prognosis. This unexpected finding was thought to be an effect of local immunological response, although no data supported this thesis. MATERIALS AND METHODS: LMVD and lymphovascular invasion (LVI) were assessed in 85 specimens of cervical cancer stage pT1b by immunostaining for podoplanin, a marker for lymphatic endothelia. Local immunological response, evident by inflammatory stromal reaction (ISR), was determined in H&E-stained slides and rated from grade 1 (absent or weak) to 3 (strong) RESULTS: A good correlation of LMVD and ISR was found (p=0.002). While a strong correlation between LMVD and the presence of LVI was found (p<0.001), no association between LMVD and pelvic lymph node involvement (p=0.732) was observed. ISR indicated favourable prognosis of patients (p=0.0247, log-rank test). CONCLUSION: Our findings suggest that ISR might play a role in the induction of lymphangiogenesis in early stage cervical cancer.
