자궁경부 이형성증과 암의 진단을 위한 액상세포 검체에서 p16INK4a/Ki-67 이중면역염색의 평가
Evaluation of p16INK4a/Ki-67 Dual Immunostaining in Liquid-based Cytology for Diagnosis of Uterine Cervical Dysplasia and Cancer
3
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
최근 p16INK4a/Ki-67 이중면역염색은 액상세포검사에서 자궁경부 이형성증과 암을 조기에 발견하기 위한 새로운 생체 표지자로 대두되고 있다. 저자들은 자궁경부질도말의 액상세포검체 총 109례에서 CINtecⓇ PLUS kit를 사용하여 p16INK4a/Ki-67 이중면역염색을 시행하였고, 그 결과를 액상세포검사, HPV hybrid capture II (HC II) 검사 그리고 조직학적 진단과 서로 비교하였다. p16INK4a/ Ki-67 양성 발현은 세포학적 진단에서 저등급 편평상피내병변 이상의 증례 그리고 조직학적 진단에서 자궁경부 상피내종양 1등급 이상의 증례에서 유의미하게 높았다. 액상세포검사상 비정형 편평상피세포 소견을 보이는 46례 중, 31례 (67.4%)가 p16INK4a과 Ki-67 양성 소견을 보였고, 이러한 양성 증례들은 조직검사에서도 대부분 자궁경부 상피내종양 1등급 이상의 병변에 해당하였다. 자궁경부 상피내종양 1등급 이상의 병변을 발견하기 위한 p16INK4a/Ki-67 이중면역염색의 민감도는 액상세포검사보다 높은 89.0%였고, 특이도는 73.5%로 HC II 검사보다 높게 분석되었다. 따라서, p16INK4a/Ki-67 이중면역염색 방법은 액상세포검사법의 민감도와 HC II 검사법의 특이도를 보완하기 위한 진단적 검사로 유용하다고 할 수 있다.
Abstract
Recently, p16INK4a/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the p16INK4a/Ki-67 dual immunostaining using a CINtecⓇ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of p16INK4a and Ki-67 was significantly asso-ciated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, p16INK4a and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of p16INK4a/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the p16INK4a/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.
참고문헌 (28)
- Byun SW, "Immunostaining of p16INK4a", Ki-67 and L1 capsid protein on liquid-based cytology specimens obtained from ASC-H and LSIL-H cases, 2013, pp.10, 1602~1607
- 김태전, "인유두종 바이러스의 감염 또는 감염되지 않은 자궁 경부 이형성증에서 p53 및 Ki-67의 발현", 대한임상검사과학회지, 36(2), pp.178~184 (2004), 대한임상검사과학회
- Dona MG, "Pescarmona E, et al. p16", Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy, 2012, pp.126, 198~202
- Edgerton N, "Evaluation of CINtec PLUS Testing as an adjunctive test in ASC-US diagnosed Surepath preparations", Diagn Cytopathol, 41, pp.35~40 (2013)
- Ikenberg H, "Screening for cervical cancer precursors with p16", Ki-67 dual-stained cytology: results of the PALMS study, 2013, pp.105, 1550~1557
- Keating JT, "Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis", Adv Anat Pathol, 8, pp.83~92 (2001)
- Keating JT, "Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia", Am J Surg Pathol, 25, pp.884~891 (2001)
- 김민영, "자궁경부종양에서 p63 발현과 다른 면역조직화학 표지자와의 비교 분석", Journal of Pathology and Translational Medicine, 37(5), pp.333~341 (2003), 대한병리학회
- Klaes R, "Overexpression of p16(INK4a) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri", Int J Cancer, 92, pp.276~284 (2001)
- Kruse AJ, "Ki-67 predicts progression in early CIN. Validation of a multivariate progression risk mode", Cell Oncol, 26, pp.13~20 (2004)
- 권민정, "세포진 검사상 ASCUS", LSIL로 저평가된 환자에서 CIN II이상의 고등급 병변을 진단하는 데 있어 hybrid capture II assay를 이용한 고위험군 HPV viral load의 유용성, 2005, pp.48(12), 2867~2876[DOI]
- 이경옥, "Genotype Frequency of Human Papillomavirus Determined by PCR and DNA Sequencing in Korean Women", 대한임상검사과학회지, 38(2), pp.99~105 (2006), 대한임상검사과학회
- 임형수, "자궁경부상피내종양 1 이상 병변의 진단에서 실시간 광전기적 기구의 유효성", Obstetrics & Gynecology Science, 53(10), pp.888~893 (2010), 대한산부인과학회
- "Annual report of cancer statistics in Korea in 2011" (2011)[URL]
- Nucci MR, "Biomarkers in diagnostic obstetric and gynecologic pathology:A review", Adv Anat Pathol, 10, pp.55~68 (2003)
- Overstad IT, "Comparison of different commercial methods for HPV detection in follow upbiopsies and spontaneous regression of CIN 2-3", Gynecol Oncol, 123, pp.278~283 (2011)
- Petry KU, "Reinecke-Luthge A, Bergeron C, et al. Triaging pap cytology negative, HPV positive cervical cancer screening results with p16", Ki-67 Dualstained cytology, 2011, pp.121, 505~509
- Reuschenbach M, "Performance of p16INK4a-cytology, HPV mRNA, and HPV DNA testing to identify high grade cervical dysplasia I women with abnormal screening results", Gynecol Oncol, 199, pp.98~105 (2010)
- Sano T, "Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions", Am J Pathol, 153, pp.1741~1748 (1998)
- Schmidt D, "p16", Ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology results from the European equivocal or midly abnormal Papanicolaou cytolgy study, 2011, pp.119, 158~166
- Stanley MA, "Prognostic factors and new therapeutic approaches to cervical cancer", Virus Res, 89, pp.241~248 (2002)
- Stoler MH, "Interobsever reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL triage study", JAMA, 285, pp.1500~1505 (2001)
- Szarewski A, "Comparison of seven test for high-grade cervical intraepithelial neoplasia in women with abnormal smears", J Clin Microbiol, pp.1867~1873 (2012)
- Wentzensen N, "Performance of p16", Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population, 2012, pp.18, 4154~4162
- Waldstrom M, "Evaluation of p16INK4a", Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with lowgrade squamous intraepithelial lesion, 2013, pp.121, 136~145
- 여소진, "ASCUS 시 ThinPrepTMsmear에서 biomarker로서의 p16INK4A의 과발현", Journal of Gynecologic Oncology, 16(2), pp.141~147 (2005), 대한부인종양학회
- Yoshida T, "Usefulness of CINtecⓇ PLUS p16", Ki-67 double-staining in cytological screening of cervical cancer, 2011, pp.55(5), 413~420
- Zappacosta R, "Chromogenic in situ hybridization and p16", Ki-67 dual staining on formalin-fixed paraffin-embedded cervical specimens: Correlation with HPV-DNA test, E6, Biomed Res Int, pp.2013, 2013[DOI]