P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma

OBJECTIVES: The purpose of this study was to determine the relation between p63, p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical carcinoma, who had undergone radiation and concurrent chemotherapy, retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996, were included in the present study. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of p63 and EGFR, which were determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed slides. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patient survival. RESULTS: Overall the indices of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and 26.6%, respectively, and these were found to be correlated. EGFR expression was significantly associated with extrapelvic failure (P = 0.03), whereas p63 was associated with locoregional failure (P = 0.03). The spontaneous apoptotic index showed no prognostic value, but the immunoreactivities of p63 and EGFR were associated with a worse prognosis by both univariate (P = 0.01 and 0.04, respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9-8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated with poor survival and locoregional failure, whereas EGFR expression was found to be a prognostic predictor of extrapelvic failure. Both molecules were found to be potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine cervix, who had received radiotherapy and concurrent chemotherapy.     

Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression

OBJECTIVE: The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and expression of p53 and c-erbB-2 proteins. METHODS: Thirty-seven cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). RESULTS: Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c-erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9 +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that did not express VEGF (P < 0.05). VEGF expression was significantly associated with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both VEGF expression and c-erbB-2 expression were similar in tumor tissues. In univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival. CONCLUSION: VEGF expression plays a role in promoting angiogenesis in cervical adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of VEGF expression.     

Ki-67 and vascular endothelial growth factor expression in uterine leiomyosarcoma

OBJECTIVE: Uterine leiomyosarcomas (LMS) are rare female neoplasms of high malignant potential. The importance of different prognostic parameters in these malignancies remains controversial. The aim of the present study was to evaluate the prognostic value of Ki-67 and vascular endothelial growth factor (VEGF) in uterine LMS. METHODS: Ki-67 and VEGF expression was assessed using immunohistochemistry from paraffin-embedded tissue in 20 patients with uterine LMS. RESULTS: Ki-67 was expressed in 10 of 20 cases (50%) of uterine LMS. A statistically significant positive correlation was observed between vascular space involvement and Ki-67 expression (P = 0.05). There was no statistically significant relationship between Ki-67 expression and clinical stage (P = 0.38), recurrent disease (P = 0.86), and age (P = 1.0). An expression of VEGF could be observed in 1 of 20 (5%) cases. The median disease-free survival was 13 months (range: 3-23 months). Eleven (55%) patients died of the disease with a median overall survival of 47.4 months (range: 1-227 months), resulting in a 5-year-overall survival rate of 45%. In a univariate analysis a statistically significant shortened disease-free survival in patients with Ki-67 positive tumors could be observed (P = 0.01). CONCLUSIONS: Our results suggest that the significant expression of Ki-67 in uterine LMS, correlating with vascular space involvement and being associated with a shortened disease-free survival, may be an indicator of the biological aggressiveness of these rare tumors.     

子宫颈癌组织中水通道蛋白8和bcl-2蛋白的表达及其相关性

目的 探讨水通道蛋白(AQP)8、bcl-2蛋白在宫颈癌组织中的表达及其相关性.方法 采用免疫组化Envision二步法检测AQP8和bcl-2蛋白在74例宫颈癌(其中鳞癌46例、腺癌28例)、34例宫颈上皮内瘤变(CIN)和15例正常宫颈组织中的表达情况,并分析两者的相关性.结果 AQP8和bcl-2蛋白主要在CIN异型细胞和宫颈癌细胞的细胞质内表达,AQP8蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为98%、61%、71%和53%,鳞癌高于腺癌、CIN和正常宫颈组织,差异有统计学意义(P＜0.01);腺癌与CIN、正常宫颈组织比较,CIN与正常宫颈组织比较,差异均无统计学意义(P＞0.05).bcl-2蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为74%、71%、53%和20%,鳞癌与腺癌组织比较,差异无统计学意义(P＞0.05);鳞癌、腺癌高于CIN、正常宫颈组织,CIN也高于正常宫颈组织,差异均有统计学意义(P＜0.01).AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关(rs=0.463,P=0.000).结论 AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关,AQP8蛋白表达上调可能与宫颈癌的发生、发展有一定的关系.     

宫颈鳞癌和腺癌中微血管密度和基质金属蛋白酶-2 、9及其抑制剂-1、2表达的研究

目的通过观察肿瘤微血管密度(MVD)及MMP-2、MMP-9和TIMP-1、TIMP-2在宫颈鳞癌与腺癌组织中的表达情况,在蛋白水平探讨宫颈腺癌较鳞癌恶性程度高的可能原因.方法采用免疫组织化学方法(SP) 检测40例宫颈鳞癌和20例宫颈腺癌组织的MVD和MMP-2、MMP-9、TIMP-1、TIMP-2蛋白的表达情况.结果MVD在宫颈腺癌中较鳞癌高.MMP-2在宫颈鳞癌的阳性表达强度较腺癌高(P=0.006);MMP-9、TIMP-1在腺癌的阳性表达较鳞癌高(P=0.078,P=0.000);TIMP-2在两组间比差异无显著性(P＞0.05).在宫颈癌的临床病理特征中,MMP-2和MMP-9在鳞癌和腺癌中的表达不一,而TIMP-1始终是在腺癌中的表达较鳞癌高.结论宫颈腺癌较鳞癌恶性程度高的原因,可能与较高的MVD和TIMP-1的高表达有关.     

Serum vascular endothelial growth factor165 levels and uterine fibroid volume

BACKGROUND: Vascular endothelial growth factor165 (VEGF165) demonstrates increased expression in uterine fibroids. This study aimed to investigate the relationship between serum VEGF165 levels and uterine fibroid volume. METHODS: On a prospective observational basis, 80 women with symptomatic uterine fibroids underwent hysterectomy. Uterine weight was determined after hysterectomy. Six hours before and 48 h after hysterectomy, serum VEGF165 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Logistic regression analysis showed no correlation between serum VEGF165 levels and uterine weight (r=0.0037; P>0.05). The mean serum VEGF165 level declined significantly from 716.31+/-457.99 to 581.81+/-403.32 pg/mL after hysterectomy (P<0.0001). Controlling for age, body mass index, uterine weight, proliferative or secretory phase, and parity, only parous patients (n=58) were found to have significantly decreased serum VEGF165 levels after hysterectomy (P=0.000035), in contrast to nulliparous patients (n=22; P=0.15). CONCLUSIONS: Serum VEGF165 levels do not correlate with uterine fibroid volume, but demonstrate a significant decrease after hysterectomy. The decrease in serum VEGF165 levels after hysterectomy was significant in parous but not in nulliparous patients with uterine fibroids. Serum VEGF165 levels may not predict uterine fibroid development.     

Flow cytometric DNA analysis of early stage adenocarcinoma of the cervix.

OBJECTIVE: The aim of this study was to determine the utility of DNA flow cytometry as a prognostic indicator for risk of recurrence and overall survival in patients with early stage adenocarcinomas of the uterine cervix. METHODS: DNA flow cytometry was performed to determine ploidy, DNA index, and proliferative index in 66 women with stage IB and IIA pure mucinous adenocarcinomas of the cervix treated by primary surgical therapy with radical hysterectomy and pelvic lymphadenectomy. Fifty-seven of 66 (86.3%) tissue samples were analyzable. Three sections were obtained from paraffin-embedded tissue blocks containing primary tumor. Flow cytometric results, along with other known prognostic variables for risk for recurrent disease and survival, were analyzed using the Cox regression proportional hazards model and survival curves generated by the Kaplan-Meier method. RESULTS: Of 57 interpretable samples, DNA ploidy patterns were 18 (27%) diploid, 8 (12%) tetraploid, and 31 (47%) aneuploid. Thirteen of 66 patients (20%) experienced recurrence with a median time to recurrence of 1.6 years. No significant correlation was noted between DNA ploidy and risk of recurrence (P = 0.429). Multivariate analysis confirmed that positive metastatic lymph nodes were associated with risk of recurrence (P < 0.001). In node-negative patients, a high proliferative index (S% + G(2)M% > 20%), measured as a continuous variable, was the only significant factor for tumor recurrence (P = 0.002). CONCLUSION: DNA ploidy does not predict a patient's risk for tumor recurrence; however, a high proliferative index value warrants further investigation as a potential prognostic indicator for risk of recurrent disease in patients with adenocarcinoma of the uterine cervix.     

Flow-cytometric DNA analysis of early stage adenocarcinoma of the cervix.

OBJECTIVE: The purpose of this study was to determine the utility of DNA flow cytometry as a prognostic indicator for risk of recurrence and overall survival in patients with early stage adenocarcinomas of the uterine cervix. METHODS: DNA flow cytometry was performed to determine ploidy, DNA index, and proliferative index in 66 women with stages IB and IIA pure mucinous adenocarcinomas of the cervix treated by primary surgical therapy with radical hysterectomy and pelvic lymphadenectomy. Fifty-seven of 66 (86.3%) tissue samples were analyzable. Three sections were obtained from paraffin-embedded tissue blocks containing primary tumor. Flow-cytometric results, along with other known prognostic variables for risk for recurrent disease and survival, were analyzed using Cox regression proportional hazards model, and survival curves were generated by the Kaplan-Meier method. RESULTS: Of 57 interpretable samples, DNA ploidy patterns were 18 (27%) diploid, 8 (12%) tetraploid, and 31 (47%) aneuploid. Thirteen of 66 patients (20%) experienced recurrence with a median time to recurrence of 1.6 years. No significant correlation was noted between DNA ploidy and risk of recurrence (P = 0.429). Multivariate analysis confirmed that positive metastatic lymph nodes were associated with risk of recurrence (P < 0.001). In node-negative patients, a high proliferative index (S% + G(2)M% > 20%), measured as a continuous variable, was the only significant factor for tumor recurrence (P = 0.002). CONCLUSION: DNA ploidy does not predict a patient's risk for tumor recurrence; however, a high proliferative index value warrants further investigation as a potential prognostic indicator for risk of recurrent disease in patients with adenocarcinoma of the uterine cervix.     

Prognostic factors in adenocarcinoma of the uterine cervix

OBJECTIVE: To determine the behaviour of adenocarcinomas of the uterine cervix during the last 10 years in the southwest region of the Netherlands, and to determine prognostic factors. METHODS: Three hundred and five cases of primary cervical adenocarcinomas (ACs) diagnosed between 1989 and 1999 in the region of Rotterdam, The Netherlands, were retrieved. Clinical and pathological data were reviewed and analysed. RESULTS: Mean age at presentation was 52 years. The mean follow-up time for surviving patients was 61 months. The overall survival was 60% at 5 years. The 5-year survival rates for stages I and II were, respectively, 79% and 37%. The 5-year survival rates for stages III and IV were less than 9%. Using univariate analysis stage, grade, age < 35 years and histological type were significant prognostic factors. In the group of patients who underwent surgery (n = 200), stages I-IIA, lymph node metastases, lymph-vascular-space-invasion (LVSI) and depth of stromal invasion were significant for survival. For patients with stages I and II-A disease, survival was significantly better where the primary treatment was surgical as opposed to primary radiotherapy (P = 0.002). Using multivariate analysis, only stage, grade and lymph node metastases remained significant independent predictors for survival. CONCLUSIONS: This report about cervical adenocarcinoma in the southwest region of The Netherlands shows similar results for survival to previous reports. Longest survival was for patients with early stage disease, younger patients and after primary surgery. We found FIGO stage, grade and lymph node metastases of significant prognostic value for survival in cervical adenocarcinoma.     

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.     

血管内皮生长因子及其受体在卵巢上皮性癌组织中的表达

目的研究血管内皮生长因子(VEGF)及其受体(FLT1、FLK1)mRNA在卵巢上皮性癌组织中的表达及与临床病理因素的相关性。方法采用逆转录聚合酶链反应技术检测70例卵巢上皮性癌及22例卵巢良性肿瘤病变组织标本中VEGFmRNA及其受体FLT1mRNA及FLK1mRNA的表达。结果在良、恶性卵巢组织中均检测到VEGF121mRNA、165mRNA的表达,在卵巢上皮性癌组织中表达水平分别为(0.452±0.134,0.301±0.096)高于良性卵巢肿瘤[0.195±0.066(P=0.000),0.204±0.059(P=0.001)];在卵巢上皮性癌组织中,VEGF121mRNA表达高于VEGF165mRNA(P=0.000),而在良性卵巢肿瘤组织中两者表达水平差异无显著性(P=0.667)。FLT1mRNA、FLK1mRNA在部分卵巢上皮性癌组织中表达,分别为38.6%(27/70)和25.7%(18/70),而在良性卵巢肿瘤组织中未见表达。卵巢癌组织中VEGF121、VEGF165、FLT1、FLK1之mRNA表达与患者年龄、肿瘤体积、淋巴结转移、肿瘤分期之间无明显相关性。结论VEGF121、165及其受体FLT1、FLK1在卵巢上皮性癌的血管生成中起重要作用。     

VEGF、MMP2、MVD与卵巢癌临床病理关系的研究

目的 :研究卵巢癌中VEGF、MMP2的表达和MVD与临床病理参数和预后的关系并探讨其临床价值。方法 :采用免疫组化技术检测 5 3例卵巢癌和 10例卵巢交界性肿瘤中VEGF、MMP2的表达水平 ,用CD34标记新生血管内皮细胞 ,在显微镜下观察血管密度。结果 :卵巢癌中MVD与年龄呈正相关 (P =0 .0 16 ) ,粘液性囊腺癌中MVD高于其它组织学类型 (P <0 .0 1)。卵巢癌中VEGF的表达与FIGO手术分期呈正相关 (P =0 .0 0 1) ,VEGF表达还与腹水量呈正相关 (P =0 .0 0 2 )。MVD与VEGF、MMP2表达呈正相关 (P值分别为 0 .0 2 1和 0 .0 31) ,VEGF表达与MMP2表达呈正相关 (P =0 .0 0 2 )。VEGF、MMP2强阳性表达和MVD较高 (≥ 10 /HP)的患者预后差 (P值分别为 0 .0 2 6 ,0 .0 36和 0 .0 38)。结论 :VEGF是重要的血管生成因子 ,MMP2不仅在肿瘤的浸润和转移中意义重大 ,而且在肿瘤的血管生成中发挥作用。卵巢癌的FIGO手术分期、MVD及VEGF、MMP2表达与预后相关 ,特别是MMP2在肿瘤的浸润、转移和血管生成中有双重作用 ,既有助于判断患者对传统治疗的敏感性 ,而且对开发针对肿瘤的生物特异性治疗具有启发作用。     

Serum CA 125 is an independent prognostic factor in cervical adenocarcinoma

OBJECTIVE: The purpose of this study was to determine the prognostic significance of a pretreatment serum CA 125 value in patients who were diagnosed with adenocarcinoma of the cervix. STUDY DESIGN: All patients who were diagnosed with adenocarcinoma or adenosquamous carcinoma of the cervix and treated definitively between 1986 and 1998 were eligible. The relationship between pretreatment serum CA 125 values and various clinical factors was evaluated. RESULTS: Seventy-three patients had pretreatment CA 125 drawn, with values that ranged from 5 to 683 U/mL and all patients were included in this study. A CA 125 value of >or=30 U/mL was defined as elevated by the receiver operating characteristic curve analysis and used for all subsequent analyses. Elevated serum CA 125 values were identified in 33% of the 73 patients. On the basis of the univariate analyses, an elevated pretreatment CA 125 value was associated significantly with advanced International Federation of Gynecology and Obstetrics stage (>IIA, P =.01), high grade (2 or 3, P =.04), tumor diameter >4 cm (P <.01), and positive pelvic or para-aortic lymph nodes (P =.002). The median survival time was 2.8 years for patients with a pretreatment CA 125 value of >or=30 U/mL and not yet reached for patients with values of <30 U/mL(P <.001). Pretreatment clinical variables that included CA 125 value, age, stage, grade, and tumor diameter were evaluated in a Cox proportional hazards model, and an elevated CA 125 value was the most significant predictor of survival (P <.001). CONCLUSION: Serum CA 125 is an independent prognostic marker for patients with cervical adenocarcinoma.     

Evaluating prognostic parameters in women with uterine leiomyosarcoma. A clinicopathologic study

OBJECTIVE: To evaluate the prognostic impact of different clinicopathologic parameters in patients with uterine leiomyosarcoma. STUDY DESIGN: Twenty-one patients with histologically proven uterine leiomyosarcoma were included in the analysis. Leiomyosarcomas were defined as uterine smooth muscle tumors with > or = 5 mitoses per 10 high-power fields and nuclear atypia and/or necrosis. RESULTS: The median follow-up time was 47 months; 5-year overall survival was 41%. A univariate Cox model revealed that early tumor stage (P = .00001), age at diagnosis < 50 years (P = .02), absence of vascular space involvement (P = .04), low myometrial invasion (P = .006) and low histologic grade (P = .04) were associated with lengthened overall survival. Adjuvant radiotherapy and/or chemotherapy (P = .1) did not influence overall survival. CONCLUSION: Early tumor stage, age at diagnosis < 50 years, absence of vascular space invasion, low myometrial invasion and low histologic grade were parameters of a good prognosis in women with uterine leiomyosarcoma. Adjuvant chemotherapy and/or radiotherapy showed no benefit in these patients.     

宫颈鳞癌与腺癌生物学行为的回顾性对比分析

目的探讨宫颈鳞癌(SCC)和宫颈腺癌(AC)在生物学行为方面存在的差异,为宫颈癌的合理诊治提供更多的临床依据。方法回顾分析山东大学齐鲁医院妇产科1997年1月至2006年3月收治的273例宫颈癌初治患者的临床资料,对比分析SCC和AC在发病相关因素、临床病理特征、5年生存率等生物学行为方面的不同。结果SCC和AC两组病例中有吸烟史者分别占22%和10%、宫颈涂片阳性率分别为80%和46%,体重指数(body mass index,BMI)≥24kg/m2者分别占15%和34%,确诊时FIGOⅠ期、Ⅱ期、Ⅲ期、Ⅳ期患者分别占SCC患者的42%、46%、11%、1%和AC患者的31%、47%、12%、10%,卵巢转移率分别为0.5%和6.7%,5年生存率分别为69.9%和50.6%,以上差异均有统计学意义(P<0.05)。结论SCC和AC在发病相关因素、临床病理特征和预后等方面均有统计学差异,SCC组有吸烟史者的比例及宫颈涂片阳性率更高,AC患者中则体重超重或肥胖者占较高比例,AC患者确诊时晚期患者较多而且更容易发生卵巢转移,预后较SCC差。     

Angiogenesis in the uterine cervix

Abstract. Abulafia O, Sherer DM. Angiogenesis in the uterine cervix.
Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.     

子宫颈腺癌184例临床及预后分析

目的 了解宫颈腺癌影响预后的相关因素。方法 １８４例宫颈腺癌中,Ⅰ,Ⅱ期行广泛全子宫切除,盆髂淋巴结清扫术,部分病例加术前后装放疗２－３次;凡盆腔淋巴结转移者,术后补充盆野外照射治疗 肿瘤侵犯宫颈深肌层者行宫颈残端野放疗。部分病例辅以ＣＡＰ及ＣＢＰ盆腔动脉灌注化疗２－４疗程。Ⅲ,Ⅳ期则多行全量放疗加动脉插管放疗。     

Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy

OBJECTIVE: The objective was to determine the prognostic significance of the immunohistochemical expressions of Bax, Bcl-2, and p53 in squamous cell carcinoma of the uterine cervix treated by radiotherapy alone. METHODS: One hundred and seventy-four cases of squamous cell carcinoma of the cervix (stage Ib-IVa) diagnosed between January 1996 and December 1998 were investigated for Bax, Bcl-2, and p53 expressions and were correlated to the patients' survival. RESULTS: The mean age of the patients was 54.1 with a range of 29-82 years. There were 23 cases with stage I (13.2%), 99 stage II (56.9%), 51 stage III (29.3%), and 1 case with stage IV (0.6%). The 5-year disease-free survival (DFS) was 70.50% and overall survival (OS) was 65.95%. Bax, Bcl-2, and p53 expressions were seen in 68.4%, 25.9%, and 77.6% of cases, respectively. In multivariate analysis by Cox's regression, age, stage, Bax, and Bcl-2 expressions appeared to be independent prognostic predictors of DFS. Bax expression was associated with good survival (hazard ratio, 0.47) while Bcl-2 expression was associated with poor survival (HR, 2.51). In addition, a combination of Bcl-2+/Bax+ was significantly associated with poorer DFS compared to Bcl-2-/Bax+ (HR 3.55). However, none of the markers or combinations was associated with OS. CONCLUSIONS: Evaluation of Bax and Bcl-2 expressions and their co-expression provide independent prognostic information for the clinical course of the disease and therefore could be developed as a prognostic indicator for cervical cancer.     

The expression of epidermal growth factor receptor, vascular endothelial growth factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human papilloma viral load and persistence of human papillomavirus after conization with negative margins

The aim of this study was to investigate the correlations between human papillomavirus (HPV) load and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk HPV clearance or persistence after conization with negative margins. The following samples were analyzed: 77 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II testing was used to detect HPV DNA. VEGF expression was significantly associated with HPV load (rho = 0.27186, P = 0.0191), while COX-2 expression was significantly and inversely associated with HPV load (rho = -0.34309, P = 0.0028). In univariate analysis, HPV load (P = 0.0112) and VEGF expression (P = 0.0274) were significantly associated with high-risk HPV clearance or persistence after conization with negative margins. In multiple regression analysis, high viral load (relative light unit/positive control > 500) and positive VEGF expression were significantly associated with high-risk HPV persistence after conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891-51.994; OR: 6.661, CI: 1.208-36.722, respectively). In conclusion, VEGF expression is related to HPV load, while COX-2 expression is inversely related to HPV load, and immunohistochemical analysis of VEGF expression and HPV viral load are a significant and an independent prognostic indicator of high-risk HPV persistence after conization with negative margins.