Positive Pelvic Lymph Node Metastasis Research Articles

Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

Impact of Genetic Variants of Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 on Uterine Cervical Cancer

Genetic variants of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) have been reported to be associated with several cancers. Until now, no study reveals the associations between lncRNA MALAT1 polymorphisms and cervical cancer (CC). The objectives of this study were to explore the correlations among MALAT1 polymorphisms and occurrence and clinicopathological parameters of CC, as well as patient 5 years survival in Taiwanese women. The study recruited 116 patients with cervical invasive cancer and 89 patients with cervical precancerous lesions, as well as 268 non-cancer control women. LncRNA MALAT1 polymorphisms rs3200401, rs619586 and rs1194338 were selected and their genotypic frequencies were defined by real-time polymerase chain reaction. Our results revealed that there are no relationships between lncRNA MALAT1 genetic variants and occurrence of CC. The independent factor among lncRNA MALAT1 genetic variants and clinicopathological parameters were positive pelvic lymph node metastasis (p=0.001, HR: 10.94, 95% CI: 2.65-45.23). In conclusions, lncRNA MALAT1 genetic variants are not related to occurrence and clinicopathological characteristics of CC and patient 5 years survival in Taiwanese women. Pelvic lymph node metastasis could independently predict the patient 5 years survival among various MALAT1 polymorphisms and clinicopathological factors in CC.

Prognostic significance of the number of metastatic lymph nodes in early cervical cancer: a retrospective study

Purpose of Investigation: To determine the significance of positive pelvic lymph node (PLN) metastasis for progression-free survival (PFS) and overall survival (OS) of patients with early cervical cancer alone and in combination with known poor prognostic factors. Materials and Methods: This study was a retrospective analysis of 245 patients with Stage 1A-IIA cervical cancer with radical hysterectomy from 1998-2014. Age, FIGO (International Federation of Gyneacology and Obstetrics) Stage, histologic type, tumor size, stromal invasion depth, PLN metastasis, metastatic PLN numbers, lymphovascular space invasion (LVSI), parametrial invasion, and vaginal resection margin status were collected. PFS and OS were evaluated in accordance with each parameter. Results: Tumor size, LVSI, and metastatic PLN numbers were independently associated with PFS. The metastatic PLN number was associated with both PFS and OS and was an important factor for poor prognosis. Conclusion: These findings may contribute to PFS and OS assessment and treatment modality decisions.

Investigation of metastasis-associated in colon cancer-1 genetic variants in the development and clinicopathologcial characteristics of uterine cervical cancer in Taiwanese women.

The objectives of this study were to define the associations among single nucleotide polymorphisms (SNPs) of metastasis-associated in colon cancer-1 (MACC1) gene, development and clinicopathological characteristics of uterine cervical cancer, and patient survival in Taiwan. Genotypic frequencies of 5 MACC1 SNPs rs975263, rs3095007, rs4721888, rs3735615 and rs1990172 were identified for 132 patients with invasive cancer, 99 with high-grade cervical intraepithelial neoplasia and 338 normal controls using real-time polymerase chain reaction. It revealed that there were no associations of these MACC1 SNPs with cervical carcinogenesis. In the meantime, cervical cancer patients with genotype GG in MACC1 SNP rs975263 tended to display more risk to have vaginal invasion than those with AA/AG (p=0.042, OR: 8.70, 95% CI: 0.81-433.22). In multivariate analysis, positive pelvic lymph node metastasis could significantly predict worse 5 years survival rate (p=0.001; HR=9.98, 95% CI=2.64-37.77) for cervical cancer patients. In conclusion, pelvic lymph node status rather than MACC1 SNPs was the only independent parameter that could significantly predict 5 years survival rate in Taiwanese women with cervical cancer.

The clinicopathological characteristic associations of long non-coding RNA gene H19 polymorphisms with uterine cervical cancer.

The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.

MicroRNA-492 overexpression involves in cell proliferation, migration, and radiotherapy response of cervical squamous cell carcinomas.

MicroRNAs (miRNAs) are small non-coding RNA that target protein-coding mRNAs at the post-transcriptional level. The aim of this study was to define the role of miR-492 in cervical squamous cell carcinomas. After microRNA profiling and comparison, we firstly detected miR-492 expression in 104 tumor tissues biopsies derived from advanced staged (FIGO IIB-IIIB) cervical squamous cell carcinoma patients before receiving concomitant chemoradiotherapy and found miR-492 expression was significantly higher in the specimens that were sensitive to concomitant chemoradiotherapy, as compared with insensitive cancer specimens (P < 0.05). Moreover, higher expression of miR-492 was associated with pelvic lymph node metastasis (LNM) (P < 0.05). Further studies illustrated ectopic miR-492 overexpression in SiHa cells promoted cell proliferation, migration, and enhanced the sensitivity of cervical cancer cells to irradiation by promoting apoptosis. In addition, we identified TIMP2 as a direct miR-492 target, which has been shown to be critical in modulating cancer cell migration and invasion. We also confirmed that miR-492 expression levels in positive pelvic LNM were much higher than negative LNM and miR-492 played a vital role in pelvic lymph node metastasis via regulating miR-492/TIMP2/MMP10 axis. In particular, miR-492 was correlated with prognosis in the subgroup of patients with negative pelvic LNM (P < 0.05) and had a promising value in predicting treatment response in the subgroup of patients with positive pelvic LNM (an AUC of 85%, 75.00% specificity, and 95.24% sensitivity). Taken together, the results suggested that miR-492 may serve as a potential biomarker for cervical cancer treatment and prognosis.

Clinical features, pathology and prognostic factors of young cervical cancer

Objective To investigate the clinical features, pathology and prognostic factors of young patients with cervical cancer less than 35 years old. Methods One hundred and twenty cases cervical cancer less than 35 years old were selected as study group, while 120 cases of cervical cancer over 35 years old as control group in the same period.The clinical features and pathology were compared between two groups and risk factors were analyzed. Results The proportion of contact vaginal bleeding, menstrual disorders, mild cervical erosion, HPV infection, and the number of pregnancy preserving ovarian surgery in study group were significantly higher than that in control group(60.8%(73/120) vs.47.5%(57/120), 30.0%(36/120) vs.11.7%(14/120), 57.5%(69/120) vs.23.3%(28/120), 81.7%(98/120) vs.60.0%(72/120), 52.5%(63/120) vs.25.8%(31/120)), the differences were statistically significant(χ2=4.30, 12.23, 29.90, 13.63, 17.91; P<0.05). The incidence of irregular vaginal bleeding in study group was significantly lower than that in control group(6.7%(8/120) vs.15.8%(19/120)), the differences was statistically significant(χ2=5.05, P<0.05). The main pathological types of two groups were squamous cell carcinoma, non squamous cell carcinoma rate in study group was significantly higher than that in control group(27.5%(33/120) vs.15.0%(18/120)), the differences was statistically significant(χ2=5.60, P<0.05). Pelvic lymph node metastasis rate in study group was 68.3%(82/120), significantly higher than that in control group(55.0%(66/120), χ2=4.49, P<0.05). Multivariate analysis of prognostic factors in young patients with cervical cancer showed that clinical stage, pathological type, depth of cervical invasion and pelvic lymph node metastasis were independent risk factors for the prognosis of young patients with cervical cancer(Wald χ2=4.02, 6.93, 8.92, 10.87; OR=3.22, 5.57, 6.84, 5.48; 95%CI=1.13-8.62, 1.24-11.75, 2.82-17.35, 1.88-12.35, P<0.05). Conclusion There are some differences in the clinical features and pathological characteristics of young patients with cervical cancer and middle-aged and elderly patients with cervical cancer.More attention should be paid on the high clinical staging, non squamous cell carcinoma, deep cervical infiltration positive pelvic lymph node metastasis patients, focus on the investigation and prevention, improve the individual treatment and prevention and control system. Key words: Cervical cancer; Clinical features; Pathology; Prognosis

Positron emission tomography with the glucose analog [18F]‐fluoro‐2‐deoxy‐D‐glucose for evaluating pelvic lymph node metastasis in uterine corpus cancer: Comparison with CT and MRI findings

The aims of this study were to investigate the ability of positron emission tomography (PET) with the glucose analog [(18)F]-fluoro-2-deoxy-D-glucose (FDG) to detect pelvic lymph node metastasis of uterine corpus cancer and to perform a retrospective comparison with computed tomography (CT) and magnetic resonance imaging (MRI) findings. Forty-six patients with uterine corpus cancer scheduled for surgery, including bilateral pelvic and/or para-aortic lymphadenectomy, were eligible for this study. CT and MRI of the pelvis and abdomen were performed in all patients within 2 weeks preceding whole-body FDG-PET. FDG-PET images were analyzed visually for objective assessment of regional tracer uptake. The sensitivity and specificity of each imaging modality for detecting pelvic lymph node metastasis were determined, respectively. Eleven (7 with myometrial invasion less than 1/2, 4 with myometrial invasion over 1/2) of the 46 patients (23.9%) were revealed to have pelvic lymph node metastasis. The sensitivity and specificity for detecting pelvic lymph node metastasis in patients with uterine corpus cancer by FDG-PET were 31.3% and 96.1% by lymph node region, respectively, and 36.4% and 91.4% by patient, respectively. No significant difference was noted among each imaging modality with sensitivity or specificity. Moreover, the sensitivity and specificity for detecting pelvic lymph node metastasis in 29 patients with endometrioid adenocarcinomas by FDG-PET were 28.6% and 96.1% by lymph node region, respectively, and 50% and 92% by patient, respectively. No significant difference was noted among each imaging modality in terms of sensitivity or specificity. Among 11 patients with pathologically positive pelvic lymph node metastasis, three out of four patients with myometrial invasion over 1/2 were diagnosed as pelvic lymph node metastasis positive by all diagnostic modalities, however, only one of seven patients with myometrial invasion less than 1/2 was diagnosed as pelvic lymph node metastasis positive by PDF-PET and CT. MRI could not detect pelvic lymph node metastasis in patients with myometrial invasion less than 1/2. We suggest that current imaging modalities including FDG-PET cannot change medical management of patients with uterine corpus cancer before surgery.

Analysis of clinicopathologic factors predicting para-aortic lymph node metastasis in endometrial cancer

The purposes of this study were to compare the relationships between para-aortic lymph node metastasis and various clinicopathologic factors to evaluate whether para-aortic lymph node dissection is necessary when treating endometrial cancer. A retrospective study was performed on 841 patients with endometrial cancer, who underwent the initial surgery at the Keio University Hospital. Clinicopathologic factors related to para-aortic lymph node metastasis significant on a univariate analysis were analyzed in a multivariate fashion using a logistic model. According to the multivariate analysis, the clinicopathologic factor most strongly related to the existence of para-aortic lymph node metastasis was positive pelvic lymph node metastasis (P < 0.01). Among the 155 patients who underwent pelvic and para-aortic lymph node dissection, the difference of 5-year overall survival by the presence of retroperitoneal lymph node metastasis was examined by Kaplan-Meier method. The prognosis was poor even if para-aortic lymph node dissection was performed in cases of positive para-aortic lymph node metastasis. In conclusion, when deciding whether to perform para-aortic lymph node dissection in patients with endometrial cancer, it is necessary to consider the pelvic lymph nodal status. If there is no pelvic lymph node metastasis, it could not be necessary to perform para-aortic lymph node dissection.

Risk factors predictive of para-aortic lymph node metastasis in endometrial carcinomas.

To identify risk factors predictive of para-aortic lymph node (PAN) metastasis in endometrial carcinomas. Sixty patients with endometrial carcinomas Stage I to III (FIGO, 1988) who each underwent a complete pelvic and para-aortic lymphadenectomy with a semiradical or radical hysterectomy, bilateral salpingo-oophorectomy, between April 1988 and March 1996, were included in this study. The relationship between PAN metastasis and clinico-pathological factors such as histological type, grade, depth of myometrial invasion (MI), vascular space involvement (VSI), cervical invasion (CI), peritoneal cytology, tumor size, pelvic lymph node (PLN) metastasis, and glutathione S-transferase pi (GST-pi) expression was examined using univariate and multivariate analysis. Seven variables--G3 grade, more than one-half MI, positive VSI, positive CI, tumor size of more than 2 cm in diameter, positive PLN metastasis, and positive GST-pi--were significantly correlated with PAN metastasis using univariate analysis. Multivariate analysis revealed that of the above 7 variables, 3 were significantly and independently correlated with PAN metastasis: more than one-half MI, positive PLN, and positive GST-pi. The relative risk of a patient with these 3 factors having PAN metastasis was 18.0 times greater than the risk for a patient without them. These variables--More than one-half MI, positive PLN, and positive GST-pi--were significantly related to PAN metastasis.

Lymph node metastasis in bladder cancer

Forty patients who had transitional cell carcinoma of the bladder with positive pelvic lymph node metastasis, treated at Chiba University Hospital between April 1975 and March 1991 were investigated to evaluate the significance of pelvic lymph node dissection. The frequency of the patients with positive lymph node was 9.1% in all patients with transitional cell carcinoma of the urinary bladder, 4.0% in the clinical T1, 3.4% in T2, 35.7% in T3a, 32.1% in T3b, 46.2% in T4, and none in Tis and Ta. Of the 40 patients, 16 underwent cystectomy pelvic lymph node dissection, 19 had biopsy of suspicious lymph nodes which turned out to be positive for metastasis, and 5 were defined by computed tomography. Pelvic lymph node dissection was performed at the common iliac, presacral, external iliac, internal iliac, and obturator nodes. In the 16 patients who underwent cystectomy with pelvic lymph node dissection, the frequency of metastasis in each nodal group was 38% in common iliac, 31% in external iliac and obturator, and 25% in presacral and internal iliac. Out of the 16 patients, eight had regional lymphatic metastasis, three had only extra regional lymph node metastasis, and five had both regional and extra regional metastasis. Three of nine patients who had single positive node had common iliac or presacral positive node without regional lymph node metastasis.