Prognostic Factors In Cervical Carcinoma Research Articles

Application of synthetic magnetic resonance imaging and DWI for evaluation of prognostic factors in cervical carcinoma: a prospective preliminary study.

To determine the values of quantitative metrics derived from synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in evaluating the prognostic factors of cervical carcinoma (CC). In this prospective study, 74 patients with pathologically confirmed CC were enrolled. Pretreatment quantitative metrics including T1, T2 and ADC values were obtained from SyMRI and diffusion-weighted imaging (DWI) sequences. The values of all metrics were compared for different prognostic features using Student's t-test or Mann-Whitney U-test. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were utilized to evaluate the diagnostic performance of quantitative variables. T1 and T2 values of parametrial involvement (PMI)-negative were significantly higher than those of PMI-positive (p = 0.002 and < 0.001), while ADC values did not show a significant difference. The area under curve (AUC) of T1 and T2 values for identifying PMI were 0.743 and 0.831. Only the T2 values showed a significant difference between the lymphovascular space involvement (LVSI)-negative and LVSI-positive (p < 0.001), and the AUC of T2 values for discriminating LVSI was 0.814. The differences of T1, T2, and ADC values between the well/moderately and the poorly differentiated CC were significant (all p < 0.001). The AUCs of T1, T2 and ADC values for predicting differentiation grades were 0.762, 0.830, and 0.808. The combined model of all metrics proved to achieve good diagnostic performance with the AUC of 0.866. SyMRI may be a potential noninvasive tool for assessing the prognostic factors such as PMI, LVSI, and differentiation grades in CC. Moreover, the overall diagnostic performances of synthetic quantitative metrics were superior to the ADC values, especially in identifying PMI and LVSI. This is the first study to assess the utility of SyMRI-derived parameters and ADC value in evaluating the prognostic factors in CC.

Alantolactone inhibits cervical cancer progression by downregulating BMI1

Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.

The eIF3a Arg803Lys genetic polymorphism is associated with susceptibility to and chemoradiotherapy efficacy in cervical carcinoma

We aimed to explore the correlations between eukaryotic translation initiation factor 3, subunit A (eIF3a) polymorphisms and susceptibility to and chemoradiotherapy efficacy in cervical carcinoma. Between August 2007 and August 2011, 176 patients with cervical carcinoma were enrolled as the case group, and 180 healthy individuals were selected as the control group. eIF3a Arg803Lys C>T genotypes were detected by hemi-nested polymerase chain reaction restriction fragment length polymorphism. All patients received chemoradiotherapy and were evaluated for efficacy. Compared with carriers of the CC genotype, carriers of the T genotype of the eIF3a Arg803Lys C>T polymorphism had a higher risk of cervical carcinoma. The eIF3a Arg803Lys C>T polymorphism was associated with tumor size, differentiation degree, Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (LNM). The overall response rate of the case group was 69.32% (122/176). The response rate of CC genotype carriers was higher compared to patients with the CT+TT genotypes. Binary-logistic regression analysis showed that tumor size, FIGO stage, LNM, and the eIF3a Arg803Lys C>T polymorphism were influencing factors for chemoradiotherapy efficacy. Univariate analysis revealed that age, eIF3a Arg803Lys C>T polymorphism, differentiation degree, FIGO stage, and LNM were prognostic factors of cervical carcinoma, and multivariate analysis showed that age ≥ 60 years, higher FIGO stage, and LNM, as well as the CT and TT genotypes of the eIF3a Arg803Lys C>T polymorphism, were risk factors related to the prognosis of cervical carcinoma. The eIF3a Arg803Lys C>T polymorphism is connected with a higher susceptibility to cervical carcinoma and may affect chemoradiotherapy efficacy in and prognosis of cervical carcinoma.

The prognostic factors in cervical carcinoma treated by radical hysterectomy combined with pelvic radiotherapy.

e15584 Background: Local regional lymp node is the main recurrence site in cervical carcinoma after radical hysterectomy. A retrospective analysis is used to evaluate the efficacy of pelvic radiotherapy and prognostic factors for stage IB-IIB (FIGO Stage) cervical carcinoma initially treated by surgery. Methods: From May 1998 to Dec 2006, a total of 77 patients of cervical carcinoma staged IB-IIB patients were eligible for this retrospective analysis. The diseases were staged IB in 20, IIA in 27 and IIB in 30 patients. All of them received external beam irradiation with 6MV X-ray 50Gy/25 fractions to pelvic field after radical hysterectomy. Overall survival rate was estimated by using Kaplan-Meier method. The prognostic factors were analyzed using univariate (Log rank) and multivariate Cox model. Results: The follow-up time was 5-152 months (median 33 months). The overall 5-year survival rate of stage IB, IIA and IIB were 79.4%, 69.8% and 51.9%, respectively. On univariate analysis, variables significantly associated with positive included age≤35 years (χ2=4.569, P=0.033), anaemia (χ2=4.806, P=0.028), stage≥IIB (χ2=6.120, P=0.013), tumor diameter ≥ 4cm (χ2=8.238, P=0.004)and pelvic lymph node metastasis (χ2=5.582, P=0.018). However in the multivariate analysis, only age ≤ 35 years (χ2=5.637, P=0.018), tumor diameter ≥ 4 cm (χ2=4.377, P=0.036) and pelvic lymph node metastasis (χ2=7.814, P=0.005) were significant factors associated with poorer prognosis. Conclusions: Postoperative adjuvant pelvic radiotherapy can improve the efficacy of patients for stage IB-IIB cervical carcinoma. Age ≤ 35 years, tumor diameter ≥ 4 cm and pelvic lymph node metastasis were confirmed as the independent prognostic factors.

DNA Ploidy is Stronger Than Lymph Node Metastasis as Prognostic Factor in Cervical Carcinoma: 10-Year Results of a Prospective Study

To improve the outcome of patients with cervical cancer, a more accurate prognostic assessment is essential. The aim of this study was to evaluate the role of tumor DNA ploidy as an independent prognostic factor in cervical carcinoma. Furthermore, we investigated whether the presence of lymph node metastasis may have a different clinical impact according to ploidy status. In a long-term prospective study, DNA ploidy was evaluated by flow cytometry from fresh tumor samples from 136 patients with cervical cancer who underwent surgery. Ploidy, lymph node metastasis, and other classical parameters were analyzed in relation to the length of disease-specific survival. Treatment modalities did not differ between patients with diploid tumors and patients with aneuploid tumors. DNA aneuploidy was found in 52 patients (38.2%). Patients with DNA-aneuploid tumors had a significantly reduced disease-specific survival (P = 0.003). Overall, the 10-year survival probability was 54% for patients with DNA-aneuploid tumors and 80% for patients with DNA-diploid tumors. Among 64 patients with International Federation of Gynecologists and Obstetricians stage I disease, the 10-year survival rates were 38.7% for the patients with DNA-aneuploid tumors and 86.3% for those with DNA-diploid tumors (P = 0.003). Overall, diploid tumors with lymph node metastasis did significantly better than aneuploid tumors with lymph node metastasis (P = 0.05). Among the patients with International Federation of Gynecologists and Obstetricians stage I disease, there was a highly significant difference between patients with diploid node-positive tumors and patients with aneuploid node-positive tumors, with no deaths from the disease in the former group in contrast with the worst outcome in the latter group (P = 0.005). By multivariate analysis, pathologic tumor stage, lymph vascular invasion, and tumor ploidy were significant and independent parameters, whereas lymph node metastasis yielded no independent information. DNA ploidy was an independent prognostic factor in cervical carcinoma. Presence of lymph node metastasis may not always have the same impact on survival but may vary according to DNA ploidy of the primary tumor.

Prognostic Value of Extracapsular Extension of Pelvic Lymph Node Metastases in Cercinoma of the Cervix Uteri

Objectives: Pelvic lymph node involvement is a well recognised prognostic factor in cervical carcinoma (CX). Limited knowledge exists about extracapsular spread (ECS) of the metastases.

Extracapsular extension of pelvic lymph node metastases is of prognostic value in carcinoma of the cervix uteri

Objectives Pelvic lymph node involvement is a well-recognized prognostic factor in cervical carcinoma (CX). Limited knowledge exists about extranodal extension of the tumor outside the lymph node capsule, i.e. extracapsular spread (ECS). Methods Two hundred fifty-six cases of surgically treated CX (FIGO stage IB1 to IIB) with pelvic lymph node involvement were evaluated regarding the occurrence of extranodal spread of the metastatic deposits outside the lymph node capsule (ECS), determined on standardized handled lymphadenectomy specimens, regarding their impact of recurrent disease and overall survival during a median follow-up time of 62 months (95% CI 51–73 months). Results ECS was seen in 30.9% (79/256) of the cases. The occurrence of ECS showed a significant correlation to advanced stage disease ( p = 0.02), the number of involved nodes ( p < 0.001) and the size of metastatic deposits ( p < 0.01). The 5-year recurrence-free survival rate in patients with ECS was significant lower compared to patients without ECS (59.7% [95% CI: 46.3%–73.2%] versus 67.2% [95% CI: 58.9%–75.5%]; ( p = 0.04). The 5-year overall survival rate was significant lower in patients with ECS (33.5% [95% CI: 20.6%–46.3%] vs. 60.5% [95% CI: 52.3%–68.6%]; p < 0.001). In multivariate analysis, tumor stage, number of involved pelvic nodes, tumor differentiation and ECS were independent prognostic factors. Conclusions The results indicate that extracapsular spread (ECS) of pelvic lymph node metastases is of prognostic impact in cervical carcinomas. A revised FIGO/TNM classification system for pelvic lymph node disease is recommended: ECS 0 = lymph node involvement without extranodal spread of the metastatic deposits and ECS 1 = lymph node involvement with extranodal spread of the metastatic deposits.

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy.

The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.

Prognostic factors in cervical carcinoma

Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediated duip-biotin nick end-labeling (TUNEL) technique. Mitotic cell were counted by HE dyeing. Results: FIGO stage and lymph node metastasis were the most important factors for evaluating prognosis in adenocarcinoma or squamous cell carcinoma. AI/MI was positively correlated with 5-year survival of cervical carcinoma. Positive expression of nm23-H1 combed with negative expression of erbB4 [nm23-H1(+)/erbB4(−)] predicted good prognosis for adenocarcinoma. In multivariable Cox regression analysis, only FIGO stage and AI/MI were into equation. Conclusion: FIGO stage and AI/MI were independent evaluating parameter for adenocarcinoma or squamous cell carcinoma.

Alteration of cyclin D1 and CDK4 gene in carcinoma of uterine cervix

Amplification and overexpression of cyclin D1 and CDK4 genes in cervical carcinoma were studied by semi-quantitative differential polymerase chain reaction assay and an immunostaining technique, respectively. Amplifications of cyclin D1 and CDK4 genes were found in 24% (27/113) and 26% (29/112) of tumors, respectively. Overexpression of cyclin D1 and CDK4 was demonstrated in 32% (21/66) and 73% (45/62) of tumors, respectively. No tumor showed CDK4 gene mutation on single strand conformational polymorphism. Sixteen percent (8/49) of the tumor specimens showed neither amplification nor overexpression. Disease stage, tumor grade and overexpression of cyclin D1 were found to be independent poor prognostic factors in cervical carcinoma.

Loss of heterozygosity in clinical stage IB cervical carcinoma: Relationship with clinical and histopathologic features

Loss of heterozygosity (LOH) has been shown to be an important prognostic factor in a variety of malignant neoplasms. The relationship between LOH and established histopathological prognostic factors in cervical carcinoma has not been examined. We studied LOH in 58 FIGO stage IB cervical cancers treated by radical hysterectomy. In a randomly selected subset of 37 of these cases, LOH was examined using markers for all 41 chromosomal arms. Seventy-six percent of the 58 cases and 95% of the extensively studied cases showed LOH at one or more loci. The three most common sites of LOH were 3p21, 6p24-p23, and 11q23.3. In the extensively studied group, LOH on 11q was associated with extensive lymphvascular space invasion ( P = .009) and less deeply invasive tumor ( P = .042). There was a trend for tumors with LOH on 11q to recur, but this was not statistically significant. No correlation between the presence of LOH on 3p or 6p and lymphvascular space invasion or tumor depth was present. There was no correlation between the number of sites of LOH or between the presence of LOH on 3p, 6p, and llq and the presence of metastatic tumor in regional lymph nodes, histologic type (squamous v nonsquamous), tumor differentiation, maximum tumor size, degree of inflammation, pattern of invasion, mitotic rate, or clinical recurrence. In summary, tumors with 11q LOH may behave in a more aggressive fashion. Future studies of LOH in cervical carcinoma should include histopathological prognostic information so that the relationship between LOH and these factors can be determined on larger numbers of patients.

The role of human papillomavirus DNAs in cervical carcinoma and risk of lymph node metastasis: association with 72-kilodalton metalloproteinase immunostaining.

The role of human papillomavirus (HPV) as a prognostic factor in cervical carcinoma is not understood completely and little is known regarding the intrinsic mechanisms involved in the metastatic process of HPV positive carcinoma. The authors evaluated HPV status with respect to clinical features in early stage cervical carcinoma, with special emphasis on lymph node spread. The authors also analyzed the relation between HPV, lymph node involvement, and 72-kilodalton (kDa) metalloproteinase immunostaining, an enzyme that cleaves Type IV collagen and may play a role in tumor metastasis. Thirty-two patients with International Federation of Gynecology and Obstetrics Stage I and IIA squamous cell cervical carcinoma treated by primary radical surgery were reviewed. Histologic grade of differentiation, tumor size, fractional depth of invasion, and lymph node spread were evaluated with respect to HPV status and 72-kDa metalloproteinase immunostaining. HPV DNA was detected by polymerase chain reaction and the primers potentially recognized at least the following HPV subtypes: 6, 11, 16, 18, 31, 33, 34, 35, 42, 51, 56, and 58. Immunohistochemical staining was performed using the avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. HPV DNA was detected in a total of 69% of cases, and HPV-16 was the most frequent type detected. HPV positive carcinomas showed a significantly higher rate of lymph node metastases than HPV negative carcinomas (45% vs. 10%; P = 0.03); similarly, 72-kDa metalloproteinase index was significantly higher (P = 0.001). These findings suggest a relation between HPV and risk of lymph node metastasis, which may be mediated by an increased production of 72-kDa metalloproteinase.

Tumor Angiogenesis as a Prognostic Factor in Cervical Carcinoma

Angiogenesis, the induction of new capillaries and venules, has been associated with tumor growth. Increased tumor size and new vessel growth may further the opportunity for tumor cells to enter the circulation and potentiate metastatic disease. To investigate if tumor angiogenesis could serve as a prognostic factor in cervical carcinoma, we counted microvessels (capillaries and venules) in 29 patients with squamous cell carcinoma of the cervix. Surgical specimens were stained for endothelial cells specifically with Factor VIII to identify all vessels. The microvessels were counted by light microscopy (per 200× field) in tumor sections with the highest population of microvessels. This was performed by two investigators without knowledge of patient outcome or extent of disease. Microvessel counts in patients with squamous cell carcinoma were significantly different from those of control subjects: 56 ± 28.9 and 16.3 ± 3.3 ( P = 0.013). There was no correlation between microvessel count and node status, parametrial involvement, depth of invasion, or gross disease. Microvessel count was significantly correlated with vascular space involvement ( P = 0.017). Four patients who developed recurrent disease within 1 year had high microvessel counts and yet were node negative and VSI negative at surgery. As shown by Folkman in breast cancer, angiogenesis may also be an independent predictor for recurrent disease in squamous cell carcinoma of the cervix. Microvessel counts could be of prognostic value in patients who do not have other risk factors for disease recurrence.

Histochemical study of estrogen and progesterone receptors in cervical carcinoma

Estrogen and progesterone receptors were determined in 56 cases of primary cervical carcinoma tissue by histochemical methods. 42.86% of the 56 cases were ER positive and 46.43% PR positive. No correlation was found between ER and PR status and age, menopausal status of the patient and clinical stage. Adenocarcinoma had significantly higher ER and PR positive rate than squamous carcinoma. Highly differentiated carcinoma had higher ER and PR positive rate than middle- and dedifferentiated carcinoma. A positive correlation between ER and PR and cellular infiltration of stroma and peritumoral reaction of fibrin was found. The patients with ER and PR positive had a significantly higher 5-year survival. ER and PR may be used as prognostic factors in cervical carcinoma.

9 Prognostic factors in cervical carcinoma: a multivariate approach

The primary aim of this study was the identification of factors known at the time of primary treatment and contributing to the risk of developing recurrent cancerous lesions. This chapter presents a multivariate approach to the identification of prognostic factors in cervical cancer. Using logistic regression analysis, a correct prediction rate of approximately 80% was reached for recurrence or death of disease. The number of lymph nodes involved, border zone and parametrial involvement, exophytic tumour growth and mitotic activity were identified as prognostic factors.

Persistence of tumor following radiation as a prognostic factor in cervical carcinoma

Persistence of tumor following radiation as a prognostic factor in cervical carcinoma

Prognostic impact of ploidy level in carcinoma of the cervix.

The single cell DNA content was analyzed by use of flow cytometry in cervical carcinoma. The study included 171 patients, Stages Ib-III. The ploidy level was calculated as a DNA index by comparison with diploid lymphocytes. Accordingly, the tumors were divided into two groups with DNA index below and above 1.5. This division proved to be important to the recurrence frequency. In all stages investigated, a statistically significant higher recurrence frequency was found in the group with DNA index above 1.5. The same relation applied concerning the survival. It is concluded that the DNA distribution is an important prognostic factor in cervical carcinoma.

Prognostic factors in cervical carcinoma: implications in staging and management.

Individualization of treatment using judicious combinations of external and intracavitary irradiation remains the cornerstone of the radiation management of carcinoma of the cervix. The inherent propensity of this cancer to either confine itself to the pelvis or else spread in a systematic and predictable manner through lymphatic channels has facilitated its therapeutic control. The treatment of most early invasive cervical carcinomas is equally advantageous using either intracavitary radium or surgery. However, certain Stage I patients have morphologic and histologic characteristics that militate against tumor control. Factors such as tumor size, depth of invasion, vascular infiltration, uterine extension, and barrel-shaped presentation affect the course of the disease and survival. A clinical-pathologic staging for cervical carcinoma incorporating the above mentioned factors into the current clinical FIGO staging system has been suggested. It aims to facilitate the recognition of those early tumors that require additional external radiotherapy. A description of the role of surgery, intracavitary and external radiation, and their combinations is included. In advanced carcinoma of the cervix, failure can be attributed to either large tumors containing cores of hypoxic cells resistant to conventional radiation therapy or to uncontrolled subclinical disease in the lymphatics at or near the border of the irradiated area. Radiotherapy combined with surgery, oxygen enhancers, infusion chemotherapy, and large particle high LET radiation has been implemented to increase local control; for distal failures, extended field irradiation of paraaortic nodes has been found to be technically feasible and well tolerated and is being studied for its effects on increased survival. The rationale for newer treatment procedures, including preliminary results and their complications, is discussed.