title: Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression.
abstract: In an attempt to understand the molecular mechanisms for the different clinical features between adenocarcinoma/adenosquamous carcinoma (AC/ASC) and squamous carcinoma (SC) of the uterine cervix, we analyzed gene expression profiles of different histological subtypes of cervical cancer. Cancer specimens and the surrounding normal tissue counterparts were separately collected from cervical cancer patients undergoing type III radical hysterectomy. Paired total RNA (cancer and normal tissues) was isolated and analyzed with cDNA microarrays containing duplicate spots of 7 334 sequence-verified human cDNA clones. Selected differentially expressed genes specific for AC or SC were further verified using real-time quantitative polymerase chain reaction (RTQ-PCR) and immunohistochemistry. Genes, including CEACAM5, TACSTD1, S100P and MSLN were upregulated in AC. Contrarily, genes involved in epidermal differentiation complex such as S100A9 and ANXA8 were upregulated in SC. Cross-validation of the results using an independent but comparable group of patients with known long-term outcomes (n = 63, median follow-up 70.3 months; range, 4-208 months) showed that the correlation between the selected 6 differentially expressed genes and histology was highly significant. CEACAM5 (p < 0.0001) and TACSTD1 (p = 0.009) were significant prognostic factors by multivariate Cox proportional hazards regression analysis. The combination of cDNA microarray, RTQ-PCR and immunohistochemical results of this study showed that it is possible to define different gene profiles for AC and SC. Moreover, TACSTD1 expression may be a novel poor prognostic factor.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.forename: Swei
authors.initials: S
authors.lastname: Hsueh
authors.forename: An-Shine
authors.initials: AS
authors.lastname: Chao
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.forename: Wei-Hsiang
authors.initials: WH
authors.lastname: Kung
authors.forename: Shang-Lang
authors.initials: SL
authors.lastname: Huang
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Chao
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Wei
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D000090204:Mesothelin; D046228:Microarray Analysis; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000715527:MSLN protein, human; D000090204:Mesothelin