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Human papillomavirus-16 L1 gene methylation as a biomarker for progression of cervical intraepithelial lesions
Gynecologic Oncology 116 (2010) 593–598
Contents lists available at ScienceDirect
Gynecologic Oncology j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y g y n o
Abstracts
Abstracts presented for the Thirty-Eighth Annual Meeting of the Western Association of Gynecologic Oncologists
Adenocarcinoma versus adenosquamous carcinoma of the cervix: A comparison of diagnostic, clinical and pathological outcomes A. Melkonyan, L. Sheibani, D. Chase, K. Tewari University of California, Irvine Objectives. Adenocarcinomas constitute up to 25% of all cervix cancers which may coincide with an increase in less well-studied variants such as adenosquamous lesions. The objective of this study was to identify differences in cervical adenocarcinoma (AC) versus adenosquamous (ASC) carcinoma. Study methods. After IRB approval, a list of all patients at UCI with AC or ASC over the last 20 years was obtained. Demographic, diagnostic, and therapeutic data was collected. Statistical significance was defined as P < 0.05. Results. Of the 106 patients identified, 74.5% (79/106) had AC while 25.5% (27/106) had ASC. The median age for AC was 47 (27–80) versus 43 (21–73) for ASC (P = 0.12). Presenting symptoms were similar and 11–13% were asymptomatic. These tumors had similar medical comorbidities, smoking and family histories. 26/79 (32.9%) of AC patients were diagnosed by Pap while 4/27 (14.8%) of ASC patients were diagnosed by Pap (P = 0.10). 7 with AC versus 0 with ASC had a history of HSIL (P = 0.06). Surgical operations performed were similar except for the 36 AC patients (45.56%) who underwent pelvic lymph node dissection versus 3.7% (1/27) of ASC patients (P < 0.001). The final stage distribution was similar between the groups (P = NS). The groups had the same proportion of well- and moderately differentiated tumors (8%) however only 5% of AC patients versus 26% of ASC patients had poorly-differentiated tumors (P < 0.001). Conclusions. The inability to detect ASC through Pap screening and the higher incidence of poorly-differentiated tumors likely contributes to this lesions' poorer prognosis when compared to AC. Future research may focus means to enhance the detection of ASC in screening. doi:10.1016/j.ygyno.2009.10.002
Human papillomavirus-16 L1 gene methylation as a biomarker for progression of cervical intraepithelial lesions J. Willner, D. Chase, M. Kalantari, K. Osann, L. Wenzel, H. Bernard, K. Tewari University of California, Irvine Obstetrics and Gynecology
Objectives. Although HPV-DNA testing allows for identification of high-risk infections, only a small subset progress to high-grade dysplasia or carcinoma. HPV-16 L1 gene methylation is an epigenetic event resulting from viral integration which can be measured via a high thru-put system. Our hypothesis is that HPV-16/18 L1 gene methylation occurs uncommonly and its detection may serve as a biomarker for high risk disease. Study methods. A pilot study was undertaken of 65 patients referred to the UCI Colposcopy Clinic for management of abnormal Pap smears. With informed consent, an additional cytologic sample was collected for HPV-subtyping and methylation analysis. Methylation of CpG residues of the HPV16 L1 gene in cervical exfoliated cells was measured via bisulfite sequencing, PCR amplification and either direct sequencing of the amplification product or sequencing of cloned amplicons. Associations were tested using the Pearson's chi-square test. Results. Of the 65 patients, 21 (32%) were HPV16-positive. HPV16-positive patients were more likely to be referred for colposcopy with a prior HSIL pap and more likely to have highgrade dysplasia on colposcopic biopsy (P < 0.05). 4/21 (19%) HPV16 lesions contained highly-methylated L1 genes and seven were sporadically methylated. None of the patients with normal histology had evidence of HPV-16 L1 methylation and all patients with highly-methylated HPV-16 L1 genes had biopsy-proven neoplasia. Conclusions. In this pilot study, those found to be HPV16-positive were more likely to have high grade pathology. The frequency of HPV16 L1 gene methylation was low which correlates with the low frequency of progressive disease. doi:10.1016/j.ygyno.2009.10.003
HER2 Overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy J. McAlpine, K. Wiegand, M. Miller, A. Adamiak, M. Koebel, R. Vang, B. Ronnett, K. Swenerton, D. Huntsman, C. Gilks, D. Miller University of British Columbia, Department of Gynecologic Oncology Objectives. The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification,
Contents lists available at ScienceDirect
Gynecologic Oncology j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y g y n o
Abstracts
Abstracts presented for the Thirty-Eighth Annual Meeting of the Western Association of Gynecologic Oncologists
Adenocarcinoma versus adenosquamous carcinoma of the cervix: A comparison of diagnostic, clinical and pathological outcomes A. Melkonyan, L. Sheibani, D. Chase, K. Tewari University of California, Irvine Objectives. Adenocarcinomas constitute up to 25% of all cervix cancers which may coincide with an increase in less well-studied variants such as adenosquamous lesions. The objective of this study was to identify differences in cervical adenocarcinoma (AC) versus adenosquamous (ASC) carcinoma. Study methods. After IRB approval, a list of all patients at UCI with AC or ASC over the last 20 years was obtained. Demographic, diagnostic, and therapeutic data was collected. Statistical significance was defined as P < 0.05. Results. Of the 106 patients identified, 74.5% (79/106) had AC while 25.5% (27/106) had ASC. The median age for AC was 47 (27–80) versus 43 (21–73) for ASC (P = 0.12). Presenting symptoms were similar and 11–13% were asymptomatic. These tumors had similar medical comorbidities, smoking and family histories. 26/79 (32.9%) of AC patients were diagnosed by Pap while 4/27 (14.8%) of ASC patients were diagnosed by Pap (P = 0.10). 7 with AC versus 0 with ASC had a history of HSIL (P = 0.06). Surgical operations performed were similar except for the 36 AC patients (45.56%) who underwent pelvic lymph node dissection versus 3.7% (1/27) of ASC patients (P < 0.001). The final stage distribution was similar between the groups (P = NS). The groups had the same proportion of well- and moderately differentiated tumors (8%) however only 5% of AC patients versus 26% of ASC patients had poorly-differentiated tumors (P < 0.001). Conclusions. The inability to detect ASC through Pap screening and the higher incidence of poorly-differentiated tumors likely contributes to this lesions' poorer prognosis when compared to AC. Future research may focus means to enhance the detection of ASC in screening. doi:10.1016/j.ygyno.2009.10.002
Human papillomavirus-16 L1 gene methylation as a biomarker for progression of cervical intraepithelial lesions J. Willner, D. Chase, M. Kalantari, K. Osann, L. Wenzel, H. Bernard, K. Tewari University of California, Irvine Obstetrics and Gynecology
Objectives. Although HPV-DNA testing allows for identification of high-risk infections, only a small subset progress to high-grade dysplasia or carcinoma. HPV-16 L1 gene methylation is an epigenetic event resulting from viral integration which can be measured via a high thru-put system. Our hypothesis is that HPV-16/18 L1 gene methylation occurs uncommonly and its detection may serve as a biomarker for high risk disease. Study methods. A pilot study was undertaken of 65 patients referred to the UCI Colposcopy Clinic for management of abnormal Pap smears. With informed consent, an additional cytologic sample was collected for HPV-subtyping and methylation analysis. Methylation of CpG residues of the HPV16 L1 gene in cervical exfoliated cells was measured via bisulfite sequencing, PCR amplification and either direct sequencing of the amplification product or sequencing of cloned amplicons. Associations were tested using the Pearson's chi-square test. Results. Of the 65 patients, 21 (32%) were HPV16-positive. HPV16-positive patients were more likely to be referred for colposcopy with a prior HSIL pap and more likely to have highgrade dysplasia on colposcopic biopsy (P < 0.05). 4/21 (19%) HPV16 lesions contained highly-methylated L1 genes and seven were sporadically methylated. None of the patients with normal histology had evidence of HPV-16 L1 methylation and all patients with highly-methylated HPV-16 L1 genes had biopsy-proven neoplasia. Conclusions. In this pilot study, those found to be HPV16-positive were more likely to have high grade pathology. The frequency of HPV16 L1 gene methylation was low which correlates with the low frequency of progressive disease. doi:10.1016/j.ygyno.2009.10.003
HER2 Overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy J. McAlpine, K. Wiegand, M. Miller, A. Adamiak, M. Koebel, R. Vang, B. Ronnett, K. Swenerton, D. Huntsman, C. Gilks, D. Miller University of British Columbia, Department of Gynecologic Oncology Objectives. The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification,