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B and ULBP1 natural killer group 2 member D (NKG2D) ligands are independent predictors of prognosis in cervical cancer
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Abstracts / Gynecologic Oncology 133 (2014) 2–207
153 — Poster Session A The diagnostic utility of HR-HPV as a predictor of cervical cancer recurrence M.C. Yu1, R.M. Austin1, J.F. Lin1, T.L. Beck2, S. Beriwal1, J.T. Comerci1, R.P. Edwards1, P. Sukumvanich1, J. Kelley1, A.B. Olawaiye1. 1Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA, 2University of Washington Medical Center, Seattle, WA, USA. Objectives: To identify the role of cervicovaginal HR-HPV testing in predicting cervical cancer recurrence. Methods: This was a retrospective study of all patients who underwent HR-HPV testing as part of their routine surveillance for cervical cancer. Demographic information such as age, body mass index (BMI), smoking status, cancer stage, initial treatment, and results of surveillance cytology were also collected. Standard statistical analyses, including chi-square test and multivariable logistic regression, were performed. All analysis was performed using IBM SPSS 19.0 (Armonk, NY). Results: A total of 134 patients were identified. Squamous cell carcinoma was the most common histology (79.9%), followed by adenocarcinoma (14.9%). The majority (69.4%) of the cohort had bulky disease (FIGO IB2 and beyond) and was treated primarily with chemoradiation and brachytherapy. Mean follow-up time was 26.4 months, and 9.7% of patients had a disease recurrence. Of patients who recurred, 46% had tested positive for HR-HPV during their surveillance compared to 11% of patients who did not recur (relative risk 4.93, P b0.05). On multiple logistic regression controlling for patient age, race, initial stage, smoking status, treatment modality, and abnormal cervicovaginal cytology during surveillance, HR-HPV status remained significantly predictive of disease recurrence (odds ratio 9.207, P b0.05, 95% CI 1.334–63.564). Using 2 X 2 table analysis, we found that while cervicovaginal cytology has limited specificity and sensitivity in predicting recurrence (Spec 53.72%, 95% CI 44.43% to 62.82%; Sens 69.23%, 95% CI 38.6% to 90.72%), the combination of cytology with HR-HPV testing increases the specificity of testing (Spec 93.39%, 95% CI 87.37% to 97.09%; Sens 38.46%, 95% CI 14% to 68.36%). Conclusions: Persistence of HR-HPV after cervical cancer treatment is a significant risk factor for disease recurrence. At present, HR-HPV testing is not routinely used during surveillance for cervical cancer, but this study suggests that large, prospective trials investigating the role of HR-HPV and cytology co-testing in cervical cancer surveillance are needed. doi:10.1016/j.ygyno.2014.03.173
154 — Poster Session A Synaptonemal complex protein 3 is a prognostic marker in cervical cancer H. Cho1, S. Kim1, D.B. Chay1, Y.T. Kim1, J.H. Kim2. 1Yonsei University College of Medicine, Seoul, South Korea, 2Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Objectives: Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, is preferentially upregulated in various cancer cells. Its onocogenic potential and clinical significance, however, have not yet been characterized. We investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. Methods: The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in NIH3T3 cells for in vitro and in vivo studies. Furthermore, we examined SCP3 expression in tumor specimens from 581 cervical neoplasias patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival.
Results: Overexpression of SCP3 promoted AKT-mediated tumorigenesis in the NIH3T3 cell line model both in vitro and in vivo. Functional studies demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenesis. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P b 0.001), and SCP3 activation was positively associated with expression of pAKT in cervical neoplasias. Survival times for patients with cervical cancer with both SCP3 and pAKT overexpression (median, 134.0 months, n = 68) were significantly shorter than those for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108), as determined by multivariate analysis (P = 0.020). Conclusions: Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possible use of SCP3 as a novel promising cancer target for cervical cancer therapy.
doi:10.1016/j.ygyno.2014.03.174
155 — Poster Session A MICA/B and ULBP1 natural killer group 2 member D (NKG2D) ligands are independent predictors of prognosis in cervical cancer H. Cho1, D.B. Chay1, S. Kim1, Y.T. Kim1, J.H. Kim2. 1Yonsei University College of Medicine, Seoul, South Korea, 2Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Objectives: NKG2D recognizes a diverse array of cellular ligands of the MIC and ULBP/RAET family and is thought to play an important role in mediating the activation of anticancer immune response. In this study, we investigated the clinical significance of NKG2D in the pathogenesis of cervical cancer. Methods: We assessed the expression of all MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G proteins in archival tumor tissue specimens from 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues via immunohistochemical staining. Results: MICA/B, ULBP1, and RAET1E expressions were higher in cervical cancer than in low-grade CIN (P b 0.001, P = 0.012, P = 0.013, respectively) and normal cervix (all P b 0.001). Among these markers, expression of ULBP1 differed significantly, depending on the patient's FIGO stage (P = 0.010) and tumor size (P = 0.045). ULBP1 expression was correlated with MICA/B (P b 0.001) and ULBP2 expression (P = 0.002) in cervical cancer. While MICA/ B + or ULBP1 + showed improved disease-free survival time (P = 0.027 and P = 0.009, respectively) compared with that of a low-expression group, RAET1E + or RAET1G + showed shorter survival time (P = 0.018 and P = 0.029, respectively). However, the ULBP1 + group showed significantly longer overall survival time (P = 0.009). Multivariate analysis indicated that MICA/B +/ ULBP1 + (HR = 0.16, P = 0.015), ULBP1 + (HR = 0.31, P = 0.024), tumor stage (HR = 3.60, P = 0.010), and lymph node metastasis (HR = 2.71, P = 0.032) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: We demonstrated that MICA/B and ULBP1 expressions are significantly increased in cervical cancer, which is consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced expression of NKG2D ligands. Furthermore, the combination of MICA/B and ULBP1 was found to be an independent predictor of survival, suggesting value in clinical assessment.
doi:10.1016/j.ygyno.2014.03.175
Abstracts / Gynecologic Oncology 133 (2014) 2–207
153 — Poster Session A The diagnostic utility of HR-HPV as a predictor of cervical cancer recurrence M.C. Yu1, R.M. Austin1, J.F. Lin1, T.L. Beck2, S. Beriwal1, J.T. Comerci1, R.P. Edwards1, P. Sukumvanich1, J. Kelley1, A.B. Olawaiye1. 1Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA, 2University of Washington Medical Center, Seattle, WA, USA. Objectives: To identify the role of cervicovaginal HR-HPV testing in predicting cervical cancer recurrence. Methods: This was a retrospective study of all patients who underwent HR-HPV testing as part of their routine surveillance for cervical cancer. Demographic information such as age, body mass index (BMI), smoking status, cancer stage, initial treatment, and results of surveillance cytology were also collected. Standard statistical analyses, including chi-square test and multivariable logistic regression, were performed. All analysis was performed using IBM SPSS 19.0 (Armonk, NY). Results: A total of 134 patients were identified. Squamous cell carcinoma was the most common histology (79.9%), followed by adenocarcinoma (14.9%). The majority (69.4%) of the cohort had bulky disease (FIGO IB2 and beyond) and was treated primarily with chemoradiation and brachytherapy. Mean follow-up time was 26.4 months, and 9.7% of patients had a disease recurrence. Of patients who recurred, 46% had tested positive for HR-HPV during their surveillance compared to 11% of patients who did not recur (relative risk 4.93, P b0.05). On multiple logistic regression controlling for patient age, race, initial stage, smoking status, treatment modality, and abnormal cervicovaginal cytology during surveillance, HR-HPV status remained significantly predictive of disease recurrence (odds ratio 9.207, P b0.05, 95% CI 1.334–63.564). Using 2 X 2 table analysis, we found that while cervicovaginal cytology has limited specificity and sensitivity in predicting recurrence (Spec 53.72%, 95% CI 44.43% to 62.82%; Sens 69.23%, 95% CI 38.6% to 90.72%), the combination of cytology with HR-HPV testing increases the specificity of testing (Spec 93.39%, 95% CI 87.37% to 97.09%; Sens 38.46%, 95% CI 14% to 68.36%). Conclusions: Persistence of HR-HPV after cervical cancer treatment is a significant risk factor for disease recurrence. At present, HR-HPV testing is not routinely used during surveillance for cervical cancer, but this study suggests that large, prospective trials investigating the role of HR-HPV and cytology co-testing in cervical cancer surveillance are needed. doi:10.1016/j.ygyno.2014.03.173
154 — Poster Session A Synaptonemal complex protein 3 is a prognostic marker in cervical cancer H. Cho1, S. Kim1, D.B. Chay1, Y.T. Kim1, J.H. Kim2. 1Yonsei University College of Medicine, Seoul, South Korea, 2Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Objectives: Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, is preferentially upregulated in various cancer cells. Its onocogenic potential and clinical significance, however, have not yet been characterized. We investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. Methods: The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in NIH3T3 cells for in vitro and in vivo studies. Furthermore, we examined SCP3 expression in tumor specimens from 581 cervical neoplasias patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival.
Results: Overexpression of SCP3 promoted AKT-mediated tumorigenesis in the NIH3T3 cell line model both in vitro and in vivo. Functional studies demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenesis. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P b 0.001), and SCP3 activation was positively associated with expression of pAKT in cervical neoplasias. Survival times for patients with cervical cancer with both SCP3 and pAKT overexpression (median, 134.0 months, n = 68) were significantly shorter than those for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108), as determined by multivariate analysis (P = 0.020). Conclusions: Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possible use of SCP3 as a novel promising cancer target for cervical cancer therapy.
doi:10.1016/j.ygyno.2014.03.174
155 — Poster Session A MICA/B and ULBP1 natural killer group 2 member D (NKG2D) ligands are independent predictors of prognosis in cervical cancer H. Cho1, D.B. Chay1, S. Kim1, Y.T. Kim1, J.H. Kim2. 1Yonsei University College of Medicine, Seoul, South Korea, 2Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Objectives: NKG2D recognizes a diverse array of cellular ligands of the MIC and ULBP/RAET family and is thought to play an important role in mediating the activation of anticancer immune response. In this study, we investigated the clinical significance of NKG2D in the pathogenesis of cervical cancer. Methods: We assessed the expression of all MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G proteins in archival tumor tissue specimens from 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues via immunohistochemical staining. Results: MICA/B, ULBP1, and RAET1E expressions were higher in cervical cancer than in low-grade CIN (P b 0.001, P = 0.012, P = 0.013, respectively) and normal cervix (all P b 0.001). Among these markers, expression of ULBP1 differed significantly, depending on the patient's FIGO stage (P = 0.010) and tumor size (P = 0.045). ULBP1 expression was correlated with MICA/B (P b 0.001) and ULBP2 expression (P = 0.002) in cervical cancer. While MICA/ B + or ULBP1 + showed improved disease-free survival time (P = 0.027 and P = 0.009, respectively) compared with that of a low-expression group, RAET1E + or RAET1G + showed shorter survival time (P = 0.018 and P = 0.029, respectively). However, the ULBP1 + group showed significantly longer overall survival time (P = 0.009). Multivariate analysis indicated that MICA/B +/ ULBP1 + (HR = 0.16, P = 0.015), ULBP1 + (HR = 0.31, P = 0.024), tumor stage (HR = 3.60, P = 0.010), and lymph node metastasis (HR = 2.71, P = 0.032) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: We demonstrated that MICA/B and ULBP1 expressions are significantly increased in cervical cancer, which is consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced expression of NKG2D ligands. Furthermore, the combination of MICA/B and ULBP1 was found to be an independent predictor of survival, suggesting value in clinical assessment.
doi:10.1016/j.ygyno.2014.03.175