MN Protein Immunolocalization in Uterine Cervix Carcinoma With Glandular Differentiation: A Clinicopathologic Study of a New Cancer-specific Biomarker

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Abstract
MN protein is the product of the newly described endogenous MN gene that is expressed in the tumorigenic phenotype of HeLa X fibroblast somatic cell hybrids. MN protein has carbonic anhydrase and putative DNA binding activity. With the exception of gastric mucosa, MN protein is expressed in neoplasia, particularly uterine cervix carcinoma, but not in benign tissue. This investigation examined the pathogenetic and prognostic significance of MN-protein immunoreactivity in uterine cervix carcinoma with glandular differentiation. Paraffin sections from 77 cervix carcinomas with glandular differentiations including 36 pure adenocarcinomas and 41 adenosquamous carcinomas were immunostained with anti-MN-protein (M-75 monoclonal proprietary; Ciba Corning Diagnostics, Alameda, CA). A total of 64.9% of cervix carcinomas with glandular differentiation exhibit MN-protein immunoreactivity localized to plasma membranes, cytoplasm, and some nuclei of neoplastic cells only, but not in adjacent benign tissue. The MN-protein staining intensity and distribution was as follows: 37.7% strong diffuse (≥ 50% cells positive), 19.5% strong focal (< 50% cells positive), and weak (7.8%). Immunoreactivity occurred in both squamous and glandular areas of adenosquamous carcinomas and was unrelated to histopathologic features. Follow-up information was available on 67 patients: 31 exhibited recurrent disease (7 pelvic, 14 distant, and 10 both) at 1–144 months (mean 37, median 14), and 36 were disease-free at 12–216 months (mean 67, median 44.5). MN-protein immunoreactivity (all positives, both standard diffuse and strong focal, or standard diffuse only) exhibited no association with clinical outcome. Recurrent disease was associated with nuclear grade (P < .001), lymphatic invasion (P < .005), size on clinical examination or pathologic evaluation (P < .005), pelvic lymph node involvement (P < .05), and clinical stage (P < .05). MN-protein immunoreactivity did not correlate with these features and did not help predict which patients would develop recurrence in the good prognosis groups. Our data show that expression of MN-protein is associated with cervix carcinoma with glandular differentiation carcinogenesis. MN-protein immunolocalization may have a diagnostic role in confirming cervix carcinoma with glandular differentiation in histologically challenging cases.

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