title: Identification of cervical cancer markers by cDNA and tissue microarrays.
abstract: The Pap test has effectively reduced the incidence and mortality of cervical cancer. However, because of the morphological basis of this test, sensitivity and specificity are less than ideal, a situation that complicates the clinical management of women diagnosed with low-grade cervical abnormalities. In an attempt to understand the molecular basis of cervical tumorigenesis and to discover molecular markers for accurate cervical cancer screening, we used cDNA microarrays containing >30,000 Unigene clones to examine the gene expression patterns of 34 cervical tissues from different clinically defined stages. It was found that global gene expression patterns separated normal cervical tissues and low-grade squamous intraepithelial lesions from cervical cancers and most of the high-grade squamous intraepithelial lesions (HSILs). Among the top 62 genes/(expressed sequence tags) that were overexpressed in tumors and HSIL tissues, 35 were confirmed using in situ hybridization on cervical tissue micorarrays. Many of these genes were overexpressed in high-grade dysplastic and malignant cervical epithelium or in stroma adjacent to the diseased tissues, with cellular proliferation and extracellular matrix-associated genes being the most common. In general, the extent of gene overexpression increased as the lesions progressed from low-grade squamous intraepithelial lesions to HSILs and finally to cancer. It is hoped that with additional development, some of these markers will improve the interpretation of cervical screening tests and provide useful information for patient management decisions.
authors.affiliation: Department of Molecular and Cell Biology, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Christine
authors.initials: C
authors.lastname: Miller
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mosher
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhao
authors.forename: Jim
authors.initials: J
authors.lastname: Deeds
authors.forename: Mike
authors.initials: M
authors.lastname: Morrissey
authors.forename: Barb
authors.initials: B
authors.lastname: Bryant
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.forename: Ron
authors.initials: R
authors.lastname: Meyer
authors.forename: Frank
authors.initials: F
authors.lastname: Cronin
authors.forename: Bobbie S
authors.initials: BS
authors.lastname: Gostout
authors.forename: Karen
authors.initials: K
authors.lastname: Smith-McCune
authors.forename: Robert
authors.initials: R
authors.lastname: Schlegel
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015533:Transcriptional Activation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers