An evaluation of the diagnostic and prognostic significance of p16INK4a/p21WAF1/Cip1 immunostaining in squamous intraepithelial lesions of the uterine cervix using liquid‐based cytology specimens |
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| Authors: | Katsunari Ishida C.T. Asuka Araki M.D. Ph.D. Masayuki Kobayashi M.D. Ph.D. Kiyomi Taniyama M.D. Ph.D. Toru Nabika M.D. Ph.D. Makoto Nagasaki M.D. Ph.D. |
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| Affiliation: | 1. Department of Clinical Laboratory, The National Hospital Organization Hamada Medical Center, Hamada, Japan;2. Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan;3. Department of Organ Pathology, Shimane University School of Medicine, Izumo, Japan;4. Department of Obstetrics and Gynecology, The National Hospital Organization Hamada Medical Center, Hamada, Japan;5. Institute for Clinical Research, The National Hospital Organization Hamada Medical Center, Hamada, Japan;6. Institute for Clinical Research, The National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan |
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| Abstract: | Human papillomavirus (HPV) infection frequently causes squamous intraepithelial lesions (SIL) of the uterine cervix and consequently gives rise to squamous cell carcinoma. It is therefore important to identify cases that potentially develop higher grades of SIL at an early stage of the disease. In this study, we thus investigated whether immunocytochemistry for p21WAF1/Cip1 and p16INK4a could be applicable in the diagnosis and the prognostic prediction of SIL in combination with genomic analyses of HPV. The genomic analysis of high‐risk HPV (hrHPV), which was done by reversed dot blotting and by in situ hybridization, and immunocytochemistry were performed on liquid‐based cytological specimens. A cross‐sectional study comprising 145 cases of NILM, ASC‐US, LSIL, and HSIL indicated that the incidence of the positive cases for p16INK4a and p21WAF1/Cip1 and hrHPV increased with the grade of SIL. A double positive status for p16INK4a and p21WAF1/Cip1 was a significant discriminator between HSIL and LSIL/NILM, even when applied in conjunction with the genomic test for hrHPV (P = 0.006 by logistic regression analysis). However, a prospective study employing 61 NILM/ASC‐US cases, revealed that the p16INK4a/p21WAF1/Cip1 immunostaining was not a significant predictor for the progression of SIL, whereas the cytological diagnosis (NILM vs. ASC‐US) and the infection status of hrHPV conferred significant effects on the prognosis. Immunostaining of p16INK4a and p21WAF1/Cip1 provides additional information on the cytological diagnosis of SIL. A further analysis using a larger population is warranted to obtain a conclusive result regarding the prognostic significance of p16INK4a/p21WAF1/Cip1 immunocytochemistry in the diagnosis of SIL. Diagn. Cytopathol. 2014;42: 125–133. © 2013 Wiley Periodicals, Inc. |
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| Keywords: | cervical intraepithelial neoplasia p16INK4a p21WAF human papillomavirus liquid‐based cytological specimen |
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