Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High-grade Squamous Intraepithelial Lesion and Prediction of Resection Margin Involvement on Conization Specimen

김태현; 한지혜; 신은; 노재홍; 김희승; 송용상                                         /Yong-Sang Song

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자료유형: 학술저널

저자정보: 김태현 한지혜 신은 노재홍 김희승 송용상 /Yong-Sang Song

저널정보: 대한암예방학회 대한암예방학회지 대한암예방학회지 제20권 제1호

발행연도: 2015.1

수록면: 70 - 77 (8page)

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Background:Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although the use of p16INK4a (p16) staining has beenproven to improve diagnostic accuracy for high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an independent recommendation for use, alone or in combination. The primary objective was to evaluate clinical utility of Ki-67and PCNA in combination with p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of three biomarkers and resection margin status of conization specimen. Methods:The expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41 CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining results were classified into four grades: 0, 1+, 2+ and 3+. Results:The expression of three biomarkers was positively associated with CIN grade. Ki-67 immunostaining did not increase the accuracy of HSIL diagnosis when combined with p16 immunostaining compared with p16 immunostaining alone. In contrast, combining the staining results for p16 and PCNA (p16 = 3+ and PCNA ≥2+) increased its specificity (66.7% vs. 75.0%, P= 0.031) without decrease of its sensitivity (98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67 immunostaining was an independent risk factor for predicting resection margin positivity(odds ratio = 6.52, 95% confidence interval 1.07-39.64). Conclusions:We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete excision

#Cervical intraepithelial neoplasia #p16INK4a #Ki-67 #Proliferating cell nuclear antigen #Conization

참고문헌 (30)

참고문헌 신청

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Massad LS / 2013 / 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors / J Low Genit Tract Dis 17:S1~S27

Darragh TM / 2013 / The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology / Int J Gynecol Pathol 32:76~115

Stoler MH / 2001 / Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study / JAMA 285:1500~1505

Reuschenbach M / 2014 / p16INK4a immunohistochemistry in cervical biopsy specimens: a systematic review and meta-analysis of the interobserver agreement / Am J Clin Pathol 142:767~772

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