Expression of p16INK4a and MIB-1 in relation to histopathology and HPV types in cervical adenocarcinoma

Abstract

A total of 101 primary cervical adenocarcinomas were analyzed for the presence of p16 INK4a and MIB-1 expression in correlation with the presence of 'high-risk' types of human papillomavirus (HR-HPV) and clinical outcome.We found that adenocarcinoma grading showed a significant negative correlation to p16 INK4a levels (p=0.001): i.e. we found less intense p16 staining in poorly differentiated tumors than in more highly differentiated tumors as well as a highly significant correlation between HPV infection and higher levels of p16 INK4a staining (p=0.00), which was similar for different HPV-types. Tumor suppressor protein p16 INK4a levels were higher in HPV positive than in HPV negative tumors. Higher levels of the proliferation marker MIB-1 were associated with poorer outcome. Higher MIB-1 levels were seen in tumors with a lower grade and higher stage at diagnosis. Moreover, MIB-1 levels seem to be higher in tumors due to infection with HPV 16 and 18 compared with HPV 45. MIB-1 may be a helpful marker in grading adenocarcinoma: a high level of expression of MIB-1 indicates a low grade of tumor, whereas high expression of p16 INK4a indicates a highly differentiated of the tumor. Thus, immunostaining for p16 INK4a appears to be a useful diagnostic tool for cervical adenocarcinoma.

Prognostic Significance of Cell Cycle- and Invasion-Related Molecular Markers and Genomic Instability in Primary Carcinoma of the Vagina

“…17,21,43,44 However, in cervical and vulvar carcinoma, there are conflicting data on the prognostic value of these proliferation markers. In cervical adenocarcinoma, high levels of Ki67 staining was associated with more advanced stage at diagnosis and low grade, 45 whereas no prognostic value of Ki67 was demonstrated in a study on squamous cell carcinoma of the cervix. 46 However, cyclin A was found to be a poor prognostic indicator for squamous cell carcinoma of the cervix.…”

Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis

“…There was data on the positive expressions of 1 or more of 17 biomarkers in endometrioid adenocarcinoma cases versus the 5 comparators 15–17, 22, 23, 25, 26, 28, 29, 30, 31, 33–35, 37–39, 40, 42–44, 47–49, 52–55, 62, 63 . A total of 5 biomarkers (ubiquitin, telomerase, CTK20, CTK7, and EMA) were compared once and only in comparison to mucinous adenocarcinoma.…”

“…There was data on the positive expression of 1 or more of 11 biomarkers in adenosquamous carcinoma cases versus the 5 comparators 15, 16, 22, 25, 28, 29, 38, 39, 40, 43, 44, 47, 48, 52, 53, 55, 62, 63 . PTEN and VILI1 were compared once and only in comparison to mucinous adenocarcinoma.…”

E6/E7 mRNA expression analysis: A test for the objective assessment of cervical adenocarcinoma in clinical prognostic procedure

“…In our previous study of cervical adenocarcinoma, we showed that levels of the tumor suppressor protein p16INK4a are higher in poorly differentiated tumors and in HPV-positive tumors than in HPV-negative tumors (16). No correlation was found between clinical outcome, stage, and histological grade in this study of patients with detectable full-length E6/E7 mRNA.…”

“…The study includes formaldehyde-fixed paraffin-embedded tumor tissue specimens from 98 primary cervical adenocarcinomas diagnosed and surgically treated at Karolinska University Hospital-Huddinge between 1992 and 2000. Clinical information from these cases has in part been previously published (16).…”