TY - JOUR
T1 - Loss of Fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease
AU - Connolly, D. C.
AU - Greenspan, D. L.
AU - Wu, R.
AU - Ren, X.
AU - Dunn, R. L.
AU - Shah, K. V.
AU - Jones, R. W.
AU - Bosch, F. X.
AU - Munoz, N.
AU - Cho, K. R.
PY - 2000
Y1 - 2000
N2 - Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Flat protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Flat protein expression might be associated with tumor progression, immunolastochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix sampies. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of pro gression to invasive carcinoma.
AB - Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Flat protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Flat protein expression might be associated with tumor progression, immunolastochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix sampies. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of pro gression to invasive carcinoma.
KW - Acid Anhydride Hydrolases
KW - Biomarkers, Tumor/biosynthesis
KW - Carcinoma, Squamous Cell/genetics
KW - Disease Progression
KW - Female
KW - Gene Expression
KW - Humans
KW - Immunohistochemistry
KW - Neoplasm Invasiveness
KW - Neoplasm Proteins
KW - Protein Biosynthesis
KW - Proteins/genetics
KW - Uterine Cervical Dysplasia/genetics
KW - Uterine Cervical Neoplasms/genetics
UR - http://www.scopus.com/inward/record.url?scp=0033818623&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000089224600019&DestLinkType=FullRecord&DestApp=WOS
M3 - Article
C2 - 10999736
SN - 1078-0432
VL - 6
SP - 3505
EP - 3510
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -