Clinical Stage Of Cervical Cancer Research Articles

Application of 18F-FDG PET/CT in the diagnosis and treatment of cervical cancer

Accurate clinical staging of cervical cancer before treatment is very important for making treatment decisions, monitoring therapy effect, forecasting the prognosis, and adjusting treatment plan. The metabolic changes in the primary tumor and metastases of cervical cancer could be clearly detected by 18F-FDG PET/CT whole body imaging, which helps to guide the clinical staging, treatment options, and is conducive to monitoring the therapeutic efficacy and prognosis. Key words: Uterine cervical neoplasms; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Detection of cervical cancer based on photoacoustic imaging-the in-vitro results.

In current clinical practice, the diagnosis of cervical cancer (CC) is mainly through the cervical screening followed by a necessary biopsy, but this method is labor consuming and expensive, and can only detect superficial lesions around the external cervical orifice. In contrast, photoacoustic imaging (PAI) is sensitive to the abnormal angiogenesis deep in the biological tissue, and may be capable for the intact scanning both around the external orifice and in cervical canal. In this paper, we for the first time put forward the photoacoustic diagnosis of CC. A total of 30 in-vitro experiments were carried out in this study, and the obtained depth maximum amplitude projection (DMAP) images were analyzed to evaluate the extent of the angiogenesis for different clinical stages of CC. Stronger absorption from the cervical lesions is observed relative to that of normal tissue. Paired t-test indicates that the difference in mean optical absorption (MOA) between normal tissue and cervical lesion has statistical significance with a confidential coefficient of 0.05. Statistical results also show that the MOAs of the cervical lesions are closely related to the severity of CC. These results imply that PAI may have great utility in the clinical diagnosis of CC.

Analyzing simultaneous positive expression of EZH2 and P53 protein to improve predictive value in cervical squamous cell carcinoma.

The current study was undertaken to investigate the predictive value of simultaneous enhancer of zeste homolog 2 (EZH2) and P53 expression in lesions of patients with cervical squamous cell carcinoma. Quantum dot double fluorescence staining was applied to detect EZH2 and P53 protein in biopsy tissue of 168 patients with cervical squamous cell carcinoma. The expression was classified into double positive (EZH2 and P53 were positively expressed), single positive (either EZH2 or P53 was positively expressed), and double negative (neither was positively expressed). The EZH2 and P53 expression, clinical stages of cervical cancer, lymph node metastasis, progression-free survival, and overall survival were analyzed. A relationship of EZH2 and P53 expression with the clinical stage of cervical cancer and lymph node metastasis was indicated. Simultaneous detection of both proteins could partly predict prognosis, consistent with previous studies' results. The current study demonstrated that the expression levels of EZH2 and P53 in tumor tissue and the proportion of cases with double-positive expression significantly increased with increasing clinical stages of cancer, also confirming up-regulated expression of EZH2 and P53 with increasing stages. These findings may suggest that the 2 proteins were involved in the development of cervical cancer, but the nature of their interaction is undefined. The increase of EZH2 and P53 expression in patients with lymph node metastasis indicated that they may be involved in metastasis of cervical cancer. Simultaneous positive EZH2 and P53 expression could improve the predictive value of a poor prognosis in cervical cancer.

Correlation of MCM2 Detection with Stage and Virology of Cervical Cancer

The highly conserved mini-chromosome maintenance proteins (MCM) are important in the initiation of DNA replication. Few studies have correlated MCM expression with the progression of cancer. (i) To analyze the expression of MCM2 in cervical cancer; (ii) to correlate MCM2 expression with the clinical tumor staging according to FIGO classification, and (iii) to relate HPV type to MCM2 expression. Tissue micro-arrays (TMA) from patients with invasive cervical cancer and controls were analyzed. Human papillomavirus (HPV) DNA detection and HPV types were determined by in situ hybridization, PCR, and sequencing. MCM2 expression was analyzed by immunohistochemistry. The most prevalent HPV types found in invasive cancer were HPV 16 (66.6%), followed by HPV 33 (11.8%), and HPV 35 (3.6%). An increased (p<0.05) expression of MCM2 was found in invasive cervical cancers compared to controls. Moreover, a strong correlation was found between the MCM2-positive cells and the presence of HPV DNA detected by in situ hybridization. No statistically significant difference was observed between MCM2 expression and FIGO stage. The present study shows that HPV-infected cells strongly express MCM2; nevertheless, our data suggests that MCM2 is not a good biomarker when comparing the different clinical stages of cervical cancer.

Immunohistochemical study of NF-κB p65, c-IAP2 and caspase-3 expression in cervical cancer

The present study aimed to evaluate the expression of NF-κB p65, c-IAP2 and caspase-3 in human cervical cancer. Immunohistochemistry was performed to determine the levels of NF-κB p65, c-IAP2 and caspase-3 expression in cervical cancer. Our study found overexpression of NF-κB p65 and c-IAP2 and reduced expression of caspase-3 in cervical cancer and cervical intraepithelial neoplasia (CIN) II-III. The expression of these molecules had no significant differences in the various clinical stages of cervical cancer, but the expression levels of NF-κB p65 and c-IAP2 in poorly differentiated tumors and metastatic lymph nodes were higher than levels in well-differentiated tumors and non-metastatic lymph nodes. By contrast, caspase-3 expression in well-differentiated tumors and non-metastatic lymph nodes was higher than that in poorly differentiated tumors and metastatic lymph nodes. Overexpression of NF-κB p65 and c-IAP2 and reduced expression of caspase-3 in cervical cancer may be important in the tumorigenesis and development of cervical cancer, and they may be useful as biomarkers to estimate progression of cervical cancer.

Association betweenIL17Polymorphisms and Risk of Cervical Cancer in Chinese Women

Interleukin-17 (IL-17) is a proinflammatory cytokine that is associated with inflammation, autoimmune disorders, and even tumors. Previous studies revealed that a large group of human malignant tumors have abnormally high IL-17 expression. In the present study, we analyzed two single-nucleotide polymorphisms (SNPs) in the IL17A (rs2275913) and IL17F (rs763780) in 311 cervical cancer patients and 463 controls using TaqMan assays. Our results indicated that the frequencies of AA genotype and A allele of rs2275913 were significantly different between the cervical cancer patients and controls (P = 0.008, OR = 1.32, 95% CI, 1.07–1.62). Stratified analyses revealed that the polymorphism of rs2275913 was also associated with positive peritumor intravascular cancer emboli and high clinical stage. The genotype and allele frequencies of rs763780 did not show any difference between patients and controls or relate to patient clinical characteristics. Collectively, these findings suggested that IL17 gene polymorphism rs2275913 was associated with the susceptibility as well as positive peritumor intravascular cancer emboli and high clinical stage of cervical cancer in Chinese women.

Evaluation of Serum Human Telomerase Reverse Transcriptase as a Novel Marker for Cervical Cancer

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of human telomerase and its rate-limiting component. The purpose of the present study was to investigate the diagnostic value of hTERT in serum of cervical cancer patients. Preoperative values of hTERT, squamous cell carcinoma antigen (SCC-ag) and cancer antigen 125 (CA 125) were measured by enzyme-linked immunosorbent assay (ELISA) in 192 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix and 38 healthy controls. Elevated pretreatment levels of hTERT were identified in 80.2% of squamous cell carcinoma and 73.8% of adenocarcinoma patients. The expression of serum hTERT was correlated with telomerase activity in cancer tissues of both histological types. Pretreatment serum hTERT levels showed a significant correlation with clinical stage, tumor size and lymph node metastasis, but not with age. Serum hTERT measurement was found to be useful in the diagnosis and assessment of clinical stage of cervical cancer, and to be superior to the conventional tumor markers. Therefore, serum hTERT is a novel and readily available marker for cervical malignancies.

Immunohistochemical assessment of the growth fraction in cervical cancers using the monoclonal antibody Ki-67; relationship to the clinical stage, histologic type and DNA content.

To assess the growth potential of cervical cancer, cell populations in proliferating cycle (%PC) were examined by an immunohistochemical technique using the monoclonal antibody Ki-67. The %PC was 31.63 +/- 16.61% in 36 cervical cancers and was significantly higher when compared to the 7.8 +/- 3.81% found in 24 samples of normal ectocervical tissues. In cervical cancer tissues, the %PC increased in accordance with progression of the clinical stage of the disease, however, the %PC was not different among the various histologic types of invasive cervical cancers. The DNA index also increased in accordance with progression of the clinical stage of cervical cancer, however, there was no correlation between the %PC and the DNA index. These results suggest that the value of %PC obtained using the monoclonal antibody Ki-67 can be used as a parameter for evaluating the growth activity of cervical cancer and for predicting biological heterogeneity in a tumor.

Cyclooxygenase-2 Gene Polymorphisms and Risk of Cervical Cancer in a North Indian Population

Single nucleotide polymorphisms in the cyclooxygenase-2 (COX-2) might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to evaluate the effects of COX-2 +8473T/C (rs5275) and -765G/C (rs20417) gene polymorphisms on the risk of cervical cancer in women of Northern India. Peripheral blood samples were collected from 200 histopathologically confirmed patients with cervical cancer and 200 unrelated, healthy female controls of similar ethnicity. Questionnaire survey was conducted to comprehend the demographic data, smoking status, and cancer stage of patients. Polymerase chain reaction-based restriction fragment length polymorphism was used to detect the genotypes of the COX-2 gene. Cyclooxygenase-2 +8473CC genotype was associated with a significantly reduced risk of cervical cancer (P = 0.036; odds ratio, 0.4; 95% confidence interval, 0.1-0.9), whereas COX-2 -765G/C polymorphism demonstrated no association. In addition, no significant association with clinical stages of cervical cancer and modulation of risk due to tobacco usage was observed in our study. Cyclooxygenase-2 +8473T/C gene polymorphism demonstrated protective effect in North Indian women. Further studies evaluating the role of COX-2 gene polymorphisms in ethnically diverse populations and a larger cohort may help in understanding the etiopathogenesis of cervical cancer in women worldwide.

The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis in cervical cancer

This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and -D were all higher in the experimental group than in the control group (P 0.05). PDGF-A and -B expression was positively related with BVD and LVD (P<0.01, R = 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (P<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (P<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.

Discrepancies between clinical staging and pathological findings of operable cervical carcinoma with stage IB–IIB: A retrospective analysis of 818 patients

Cervical cancer is the only gynaecological cancer that is staged clinically. The clinical stage of cervical cancer relies largely on the pelvic examination. The aim of this study is to analyse the discrepancy between clinical stage and pathological results, and to explore the accuracy of pelvic examination. We collected retrospective data from 818 patients with cervical carcinoma staged IB-IIB, who were treated with primary surgery from January 1999 to June 2007. Clinical stages of those patients were determined by pelvic examination without anaesthesia. After surgery, all the patients were assigned to pT category according to the pathological findings. Comparisons were made between these two stages. The total concordance between clinical stage and pT category for stage IB-IIB was 53.1%, with an overestimation of 37.3% and an underestimation of 9.7%. The concordance in stage IB1, stage IB2, stage IIA and stage IIB were 85.4%, 77.4%, 35.3% and 20.5%, respectively. The most significant discrepancy was caused by the failure to detect the parametrial invasion accurately in stage IIB. The accuracy of pelvic examination to determine vaginal and parametrial disease was 70.2% and 74.0%, respectively. There are significant discrepancies between clinical stage and pathological results. Pelvic examination has its limitations in staging determination. Thus for operable cervical cancer, clinical stage alone is not reliable for selecting postoperative therapies and surgical staging system may be considered.

Color Doppler in the assessment of cervical cancer

The treatment and prognosis of cervical cancer depends on the clinical stage based on the FIGO classification and the presence of lymph node metastases. Clinical staging of cervical cancer does not attain a good diagnostic performance, since it is incorrect in approximately one‐third of patients who undergo surgical staging. Magnetic resonance (MR) imaging resulted to be superior to clinical evaluation and computed tomography (CT) in parametrial evaluation and in the staging of uterine cervical carcinoma. Endoluminal ultrasound was introduced to analyse the cervix but no improvement in the diagnostic accuracy with respect to clinical staging was obtained. Color Doppler velocimetry was proposed as a non‐invasive tool in the examination of cervical cancer. Cervical cancers with detectable intratumoral blood flow were associated with larger size, invasion of parametrium, pelvic lymph node metastases and greater microvessel density. A ‘vascularity index’ resulted to be correlated with staging and lymph node metastases. The aims of our study were to assess color Doppler characteristics of 48 cervical cancers at different stages and to analyse the correlation between Doppler parameters and clinical–pathological features of the tumors. Three‐dimensional color power Doppler technique was used to investigate the vascular architecture of the neoplastic tissue. Three‐dimensional vascular images were compared to magnetic resonance results. The actual clinical application of the three‐dimensional vascular analysis in the evaluation of cervical cancers remains still to be defined.

Immunologic Diagnosis and Monitoring of Cervical Cancers Using in Vitro Translated HPV Proteins

E6 and E7 proteins, the transforming proteins of oncogenic HPVs, are known to be associated with the occurrence of cervical cancer. In radioimmunoprecipitation assays in which in vitro-transcripted and translated HPV-16 E6 and E7 proteins were used, patients with HPV-16-associated invasive cervical cancer (group I) had greater seroreactivity than patients in most of the other groups, including patients with invasive cervical cancer who were infected with other types of HPVs (group II), cervical cancer patients with nondetectable HPVs (group III), patients with HPV-16-associated cervical intraepithelial neoplasia (group IV), and unaffected normal controls with noncervical lesions (group V) (P < 0.05). The sera of patients in group I, when compared with the sera of other groups, were significantly reactive with one and/or two proteins (P < 0.05). Antibodies to HPV-16 E6 and E7 proteins were detected in patients with invasive cancer more than in those with CIN. The positive rates for E6 protein were 4.2% (1/24), 43.8% (7/16), 57.1% (8/14), 100% (5/5), and 100% (1/1), and the positive rates of E7 protein were 4.2% (1/24), 12.5% (2/16), 35.7% (5/14), 60% (3/5), and 100% (1/1) from CINs through stages I, IIa, IIb, and III of HPV-16-associated cervical cancers, respectively. The positive rates for E6 and E7 proteins were significantly increased with the advancing of the clinical stages of cervical cancer (P < 0.05 for E6 and E7). To examine the change in antibody titers of HPV-16 E7 protein during diagnosis, treatment, and follow-up, we tested serial serum samples from 14 patients of group I. The antibody titers were correlated to the clinical course of disease in some cases. The positive levels of E7 antibody were decreased when the treatment was effective, but in 1 patient who had shown recurrence or progression, positive seroreactivity was maintained. Antibodies to HPV-16 E6 and E7 proteins might be effective virus-specific and disease state-specific markers of HPV-16-associated cervical cancer.

Comparison between abdominal and laparoscopic lymphadenectomy

In cervical cancer the pathologic stage is determined for two reasons: choice of treatment (surgical-radiotherapy-medical) and prognostic evaluation. In early cervical carcinoma the evaluation of pelvic lymph nodes is important. The clinical noninvasive approach using ultrasound, CT, MRI, and lymphography is of limited use because of low accuracy. Therefore, the clinical evaluation has to be performed surgically. This is required in FIGO I and FIGO IIa carcinoma with circumference < 4 cm. If the pelvic nodes are negative a radical hysterectomy is indicated; but if the nodes are positive, this procedure could be avoided and the treatment of choice is pelvic radiotherapy. In some cases radical hysterectomy is performed when the pathology of the lymph nodes is not yet known and subsequent pelvic radiotherapy is performed when the nodes are positive. This sequence of events is a major cause of complications (fistula of the intestinal or the urinary tract, ileus and lymphocysts). Laparoscopic lymphadenectomy may be the method of choice to stage these tumors with minimal discomfort for the patients. This study demonstrates that laparoscopic lymphadenectomy is comparable to open lymphadenectomy in the clinical staging of cervical cancer.

Endoluminal ultrasound staging of cervical cancer

Clinical staging of cervical cancer is incorrect in approximately one-third of patients who undergo surgical staging. Pretreatment laparotomy is the staging method of choice for patients with cervical cancer at Memorial Sloan-Kettering Cancer Center. We performed transabdominal, transvaginal, and transrectal ultrasound staging on 12 patients. In 5 of 6 patients undergoing radical hysterectomy, clinical ultrasound and surgical staging were consistent. One patient could not tolerate rectal probe sonography. Ultrasound staging was correct in 1 of 6 patients with advanced disease. A new technique of cervical imaging with transrectal ultrasound and vaginal douche is described. We believe it unlikely that ultrasound will improve the accuracy of clinical staging in patients with cervical cancer.

Magnetic resonance imaging in cervical cancer: A basis for objective classification

Abstract Conventional clinical staging of cervical cancer is subjective because it is based on palpatory findings and inadequate because it cannot assess the single most important prognostic factor—tumor size. To determine the exactitude of in vivo MRI measurements of tumor volume, 22 patients with invasive cervical cancer were studied before surgery. The volumes obtained by MRI correlated well ( r = 0.983) with those obtained by histomorphometric analysis of the surgical specimens, but only weakly with clinical stage. MRI may provide a basis for precise classification of cervical cancer and for objective comparison of surgery and radiotherapy.

Magnetic resonance imaging in cervical cancer: A basis for objective classification

Conventional clinical staging of cervical cancer is subjective because it is based on palpatory findings and inadequate because it cannot assess the single most important prognostic factor—tumor size. To determine the exactitude of in vivo MRI measurements of tumor volume, 22 patients with invasive cervical cancer were studied before surgery. The volumes obtained by MRI correlated well ( r = 0.983) with those obtained by histomorphometric analysis of the surgical specimens, but only weakly with clinical stage. MRI may provide a basis for precise classification of cervical cancer and for objective comparison of surgery and radiotherapy.

Immunocytological Distribution of the Tumor Antigen

AbstractSerum levels of the cervical cancer associated antigen (TA‐4) have been well correlated with clinical staging of cervical cancer and the response to surgery or radiation therapy. We studied immunohistologically the distribution of TA‐4 in normal and neoplastic cervical tissue. TA‐4 was localized to epithelial tissue of the uterine cervix. During squamous maturation of the cervix, TA‐4 was expressed first in the nucleus and then in the cytoplasm of the original epithelium or the columnar epithelium with squamous metaplasia. Therefore, TA‐4 seems to be associated with squamous maturation or metaplasia. The intensity of TA‐4 staining in neoplastic regions was greater than in normal epithelium. Thus TA‐4 might be related to carcinogenesis of the cervix.

Estimation of type-specific neutralizing antibody to herpes simplex virus type 2 in uterine cervical cancer patients by a new absorption method.

A simple method of estimating type-specific neutralizing antibody to type 2 herpes simplex virus (HSV-2) was devised with the use of the microneutralization system. Serially diluted serum was mixed in the well with a constant amount of type 1 virus (HSV-1), and after 3 days' incubation at 37 C, the plate was irradiated with ultraviolet light. The absorbing HSV-1 consisted of culture fluid plus an extract of infected Vero cells not especially concentrated. The well then received indicator HSV-1 or HSV-2, and after being left at 37 C for 1 hr a suspension of dispersed Vero cells was dropped into the wells, following our standard neutralization procedure. Preliminary tests with rabbit antisera showed that even a low level of HSV-2 antibody was detected by this method, unless an exceptionally high titer of HSV-1 antibody originally coexisted with the HSV-2 antibody. Sera from acutely infected persons testified to the specificity of the antibody so detected. It was revealed by means of the new technique that the rate of HSV-2 antibody was significantly higher in uterine cervical cancer patients than in control women. There was no correlation between the clinical stage of cervical cancer and the presence of HSV-2 antibody.

Histochemical Study of β-Glucuronidase in the Uterine Cancers

The histochemical observation of β-glucuronidase in 45 cases of uterine cancer was carried out in fresh frozen sections by Seligman's method, utilizing 6-bromo-2-naphthyl-β-D-glucuronide as the substrate. In squamous cell carcinomas of the cervix, moderate enzymatic activity was observed in the cancer cells. This activity was higher than that of normal squamous epithelium. In adenocarcinoma of the body and the cervix, intense enzymatic activity was observed in the cancer. This was stronger than that of normal endometrium. The enzymatic activity of adenocarcinoma were generally higher than that of squamous cell cancers. Enzymatic activity in the stroma of cancer tissue was mainly slight. There were no correlation between enzymatic activity and the clinical stage of cervical cancer, and correlation between the enzymatic activity of the cancer tissue and frequency of delivery.