Evaluation of the HPV ISH Assay in Cervical Cancer
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background : Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. Methods : The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16INK4a, p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. Results : High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. Conclusions : Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.
Abstract
Background : Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. Methods : The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16INK4a, p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. Results : High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. Conclusions : Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.
참고문헌 (27)
- Peitsaro P, "Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique", J Clin Microbiol, 40, pp.886~891 (2002)
- Gallo G, "Study of viral integration of HPV-16 in young patients with LSIL", J Clin Pathol, 56, pp.532~536 (2003)
- Badaracco G, "HPV16 and HPV18 in genital tumors:significantly different levels of viral integration and correlation to tumor invasiveness", J Med Virol, 67, pp.574~582 (2002)
- Wentzensen N, "Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract", Cancer Res, 64, pp.3878~3884 (2004)
- Dabi´c MM, "Comparison of polymerase chain reaction and catalyzed signal amplification in situ hybridization methods for human papillomavirus detection in paraffin-embedded cervical preneoplastic and neoplastic lesions", Arch Med Res, 35, pp.511~516 (2004)
- Guo M, "Evaluation of a commercialized in situ hybridization assay for detecting human papillomavirus DNA in tissue specimens from patients with cervical intraepithelial neoplasia and cervical carcinoma", J Clin Microbiol, 46, pp.274~280 (2008)
- Keating JT, "Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis", Adv Anat Pathol, 8, pp.83~92 (2001)
- Conesa-Zamora P, "Effect of human papillomavirus on cell cycle-related proteins p16,Ki-67,Cyclin D1,p53,and ProEx C in precursor lesions of cervical carcinoma:a tissue microarray study", Am J Clin Pathol, 132, pp.378~390 (2009)
- Reagan JW, "Histologic types and prognosis of cancers of the uterine cervix", Int J Radiat Oncol Biol Phys, 5, pp.1015~1020 (1979)
- Kalof AN, "p16INK4A immunoexpression and HPV in situ hybridization signal patterns:potential markers of high-grade cervical intraepithelial neoplasia", Am J Surg Pathol, 29, pp.674~679 (2005)
- Kruse AJ, "Low-and high-risk CIN 1 and 2 lesions:prospective predictive value of grade,HPV,and Ki-67 immuno-quantitative variables", J Pathol, 199, pp.462~470 (2003)
- Qiu AD, "HPV prevalence,E6 sequence variation and physical state of HPV16 isolates from patients with cervical cancer in Sichuan,China", Gynecol Oncol, 104, pp.77~85 (2007)
- Bolick DR, "Laboratory implementation of human papillomavirus testing", Arch Pathol Lab Med, 127, pp.984~990 (2003)
- 정은선, "자궁경부 상피내병변에서 사람유두종바이러스 제자리부합법 및 L1 피각단백 면역조직화학염색의 임상적 유용성", Korean Journal of Obstetrics and Gynecology, 52(12), pp.1279~1286 (2009), 대한산부인과학회
- Andersson S, "Type distribution,viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer(CIN)", Br J Cancer, 92, pp.2195~2200 (2005)
- Fontaine J, "High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV", AIDS, 19, pp.785~794 (2005)
- Ho CM, "Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer,and high viral loads predict risk of cervical cancer", Gynecol Oncol, 102, pp.54~60 (2006)
- Lorenzato M, "Cell cycle and", or proliferation markers:what is the best method to discriminate cervical high-grade lesions?, 2005, pp.36, 1101~1107
- Cameron RI, "Immunohistochemical staining with MIB1,bcl2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia,endometriosis and microglandular hyperplasia", Histopathology, 41, pp.313~321 (2002)
- Davidson B, "Expression of topoisomerase II and Ki-67 in cervical carcinoma--clinicopathological study using immunohistochemistry", APMIS, 108, pp.209~215 (2000)
- Keating JT, "Ki-67,cyclin E,and p16INK4 are complimentary surrogate biomarkers for human papilloma virusrelated cervical neoplasia", Am J Surg Pathol, 25, pp.884~891 (2001)
- McCluggage WG, "Monoclonal antibodies Ki-67 and MIB1 in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ in formalin-fixed material", Int J Gynecol Pathol, 14, pp.209~216 (1995)
- Zhao FX, "Relationship among HPV16 infection and Expression of hTERT,p21waf1,Ki67 in cervical intraepithelial neoplasias and squamous cell carcinomas of cervix uteri", Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 19, pp.370~374 (2005)
- Carrilho C, "Characterization of human papillomavirus infection,P53 and Ki-67 expression in cervix cancer of Mozambican women", Pathol Res Pract, 199, pp.303~311 (2003)
- Liang XH, "Bcl-2 protooncogene expression in cervical carcinoma cell lines containing inactive p53", J Cell Biochem, 57, pp.509~521 (1995)
- Grace VM, "Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix", Gynecol Oncol, 91, pp.51~58 (2003)
- Pillai MR, "The presence of human papillomavirus-16", -18 E6,p53,and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer, 1996, pp.5, 329~335