EXPRESSION OF THE MN ANTIGEN IN CERVICAL PAPANICOLAOU SMEARS IS AN EARLY DIAGNOSTIC BIOMARKER OF CERVICAL DYSPLASIA

A new tumor-associated antigen, MN, has been shown to be expressed in virtually all cervical carcinomas and the majority of cervical intraep ithelial neoplasia, but not in normal cervices (S, Y, Liao et al., Am, J, Pathol,, 145: 598-609, 1994), Therefore, we postulated that the ex foliative cells in cervical Papanicolaou (Pap) smears would reflect th e MN immunoreactivity seen in the tissue sections, and high levels of MN expression in the exfoliative cells would indicate the presence of dysplasia in the cervix, A total of 305 cervical Pap smears, with hist ological confirmation, representing all categories of the Bethesda Sys tem, were immunohistologically examined. We found that high levels of MN expression in exfoliative cells were not restricted to the dysplast ic cells but were observed also in the normal endocervical cells (NECs ) when dysplasia was present in the tissue biopsies. Overall, the rate s of positive MN immunostaining of the dysplastic cells in low- and hi gh-grade squamous intraepithelial lesions and invasive carcinoma were 35 (65%) of 54, 44 (77%) of 57, and 12 (92%) of 13, respectively, Howe ver, diffuse MN immunoreactivity of the atypical and/or dysplastic end ocervical columnar cells was seen in all cases (100%) of adenocarcinom a in situ (AIS; n = 23) and adenocarcinomas (II = 8), In the groups wi th cytological diagnoses of atypical squamous cells or atypical glandu lar cells of undetermined significance (ASCUS and AGUS, respectively), MN positivity was seen in 47% of ASCUS (22/47) and 55% of AGUS (12/22 ), Dysplastic tissues were identified in all MN-positive cases, In con trast, all MN-negative atypical Pap smears were confirmed histological ly to be benign cervix with one exception, in which the cytological di agnosis was ASCUS and focal low-grade squamous intraepithelial lesions were found in the cervix, The study also included 89 cases with cytol ogical diagnoses of within normal limits/benign cellular changes, Amon g these, 10 Pap smears expressed diffuse MN antigen in the NEC, and dy splasia (8 cases of low-grade squamous intraepithelial lesions, 2 AIS) was found in the cervices, None of MN-negative cases with ''within no rmal limits'' cytology contained dysplastic cervices, Therefore, it wo uld seem that diffuse MN antigen expression in the NEC may be an indic ator of cervical dysplasia, Thus, MN antigen might serve as an early b iomarker of cervical neoplasia, The combination of detection via cytol ogy and MN immunostaining resulted in no false negatives and also disc riminated between cellular atypia due to benign reactive changes versu s cellular atypia due to dysplasia in the category of ASCUS and AGUS, In particular, it was found in the AGUS group that diffuse MN immunost aining restricted to atypical columnar cells was diagnostic for AIS, T hese findings indicate that MN antigen expression is an important diag nostic biomarker of glandular neoplasia and a valuable adjunct to cyto logical diagnosis of ASCUS and AGUS.