Uterine Cervical Adenocarcinoma Research Articles

Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells.

Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling in vitro. Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.

Uterin Serviks Kanserinin Atipik Prezentasyonu: Olgu Sunumu

Increases of uterine cervical adenocarcinoma incidence have been observed in recent years. In this report, we present a rare case of cervical adenocarcinoma, which mimics vesicovaginal fistula. A 40- year-old multigravida patient presented with involuntary leakage of urine that began 6 months ago following dilatation and curettage for her pregnancy with missed abortion. During pelvic examination, exfoliation of perineum as a result of sustained exposure of wetness was observed but the ‘cough stress test’ was negative and nulliparous healthy cervix with clear watery discharge was also observed. Laparotomy with total abdominal hysterectomy and abdominal washing were done. Histological examination revealed diagnosis of cervix adenocarcinoma without lymphovascular and perinueronal invasion and also endometrial adenocarcinoma located on two different focuses without myometrial invasion. An effusive watery vaginal discharge that evaluated mistakenly as urine may be produced by the malignant gynecological adenocarcinoma.

Tumor-infiltrating CD204+ M2 macrophages compared to T cells as a prognosticator for patients with uterine cervical adenocarcinoma.

5527Background: Uterine cervical adenocarcinoma is rare but its incidence has been increasing gradually, which has a poor prognosis despite early detection. The tumor microenvironment plays importa...

Biology and treatment of cervical adenocarcinoma.

Uterine cervical adenocarcinoma (ADC) has been increasing in its prevalence world widely despite the decrease of squamous cell carcinoma (SCC). It comprises nearly 20-25% of the all cervical malignancy in developed countries. The worse biological behavior had been reported in patients with intermediate- and high risk factors after surgery, and in advanced stage over Ⅲ, radiotherapy (RT) alone and concurrent chemo-radiotherapy (CCRT) with cisplatin was not always effective. As for chemotherapy (CT), the induction CT has not established, as well. Further molecular targeted therapy (MTT) has been studied. The targets of oncogenic driver mutations were vascular endothelial growth factor (VEGF) in SCC, or tyrosine kinase (TK) of endothelial growth factor receptor 2 (EGFR2, Her2/neu)-Ras-MAPK-ERK pathway. Bevacizumab (Bev, anti-VEGF monoclonal antibody) is considered as one of key agent with paclitaxel and carboplatin in SCC, but not for ADC. This article focuses on up-to-date knowledge of biology and possible specific therapeutic directions to explore in the management of cervical ADC.

Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report

BackgroundThe vast majority of uterine cervical malignancies are primary carcinomas, and secondary neoplasms that metastasize to the uterine cervix from a distant organ are uncommon. Although relatively rare, metastases to the uterine cervix from a primary colon cancer have been reported. We report a rare case of metastatic carcinoma originating from a cecal adenocarcinoma with an unusual cytokeratin 7/cytokeratin 20 immunophenotype.Case presentationA 74-year-old postmenopausal Japanese woman was referred to our hospital for the evaluation of a uterine tumor. She had a past medical history of cecal cancer and had undergone laparoscopically assisted right hemicolectomy at the age of 69 years. During follow-up, she was found to have elevated levels of the tumor markers carbohydrate antigen 19-9 (179.7 IU/mL) and carcinoembryonic antigen (26.9 μg/L). Positron emission tomography/computed tomography showed a focus of high 18F-fluorodeoxyglucose uptake in her uterus. Examination of a cervical biopsy found a poorly differentiated adenocarcinoma that was immunopositive for cytokeratin (CK)7 and caudal-related homeobox 2 (CDX2) expression and immunonegative for cytokeratin 20 expression. The patient underwent radical hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination found invasive growth of irregular and atypical ductal hyperplasia. Immunohistochemical staining of the tumor specimen revealed the same immunophenotype as the biopsy specimen. The cecal cancer specimen from her previous surgery was also examined and found to have the same immunophenotype. The histopathological diagnosis was cecal adenocarcinoma metastatic to the uterine cervix. The patient is currently receiving adjuvant chemotherapy and to date is without evidence of recurrent disease.ConclusionsOur report illustrates the importance of immunohistochemistry for the correct diagnosis of the origin of a uterine cervical adenocarcinoma in a patient with a medical history of colorectal cancer. Re-examination of a previous oncological specimen is critical for cases with a uterine lesion that is difficult to identify as primary or metastatic cancer.

Adenocarcinoma of the uterine cervix: why is it different?

Adenocarcinoma (AC) of the uterine cervix is the second most frequent tumor type following squamous cell carcinoma (SCC). According to the National Comprehensive Cancer Network (NCCN) guidelines, there is no difference in the treatment strategy between SCC and AC. However, there are a number of studies that suggest a worse prognosis for AC compared to SCC. In this comprehensive review, we will try to find the reason why AC is different from SCC, and then discuss what we need to do to improve the prognosis of AC. Uterine cervical AC is clearly different from SCC based on its molecular pathogenesis, histological appearance, and clinical behavior. Therefore, it will be necessary to make a different treatment strategy, particularly for patients with locally advanced and metastatic or recurrent disease. It is most important to intensify our research into the molecular profile of AC, so that we can develop more appropriate targeted therapies. Because of its rarity, international collaboration among clinical trials with translational components will be key to increasing cure rates and improving survivorship.

Minimal deviation mucinous adenocarcinoma of the uterine cervix that proved difficult to differentiate from endometrial cancer: A case report.

Minimal deviation adenocarcinoma (MDA), also known as adenoma malignum of the uterine cervix, accounts for only ~1% of uterine cervical adenocarcinomas. Adenoma malignum of the uterine cervix was initially described by Gusserow in 1870. Using magnetic resonance imaging (MRI), MDA appears as multilocular lesions with solid components that extend from the endocervical glands to the deep cervical stroma. Cytological evaluation and biopsies have low detection rates, therefore, it is difficult to diagnose MDA accurately prior to treatment. The current study describes a rare case of MDA that was difficult to differentiate from endometrial adenocarcinoma of the corpus uteri preoperatively, as the endometrial biopsy results suggested a well-differentiated endometrioid adenocarcinoma and MRI did not show typical images for MDA. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the diagnosis of endometrial cancer, and the mass was subsequently diagnosed as MDA of the uterine cervix by pathological examination of the hysterectomy specimen. Postoperatively, although two types of adjuvant chemotherapy were performed, the remaining tumor continued to grow, causing obstruction of the bilateral ureters and leading to bilateral hydronephrosis. The patient is currently alive with the disease 10 months following the surgery.

Pattern of human papillomavirus infection in uterine cervical adenocarcinoma in a university hospital setting in Malaysia

Adenocarcinoma of the uterine cervix is fast gaining prominence with the worldwide decreasing trend of squamous and adenosqua-mous carcinoma. Most human papillomavirus (HPV) type-specific prevalence studies however do not specifically address this increasingly important histological type. Hence a study was conducted at the Department of Pathology, University of Malaya Medical Centre, to interrogate the HPV type-specific prevalence in 51 consecutive cases of histologically-confirmed, formalin-fixed, paraffin-embedded cervical adenocarcinoma. Prior to HPV testing all cases were subjected to amplification of a 268-bp human beta-globin fragment to ensure extracted DNA integrity. Specific HPV types were determined using the commercially available Hybribio 21 HPV GenoArray test kit which incorporates amplification and flow-through hybridisation with HPV type-specific probes. Furthermore, all HPV-negative cases were amplified using consensus L1 ORF (MY09/11) primers. Patients' ages ranged between 14-75 years (mean 48 years). Ethnically 21 cases were Malay, 20 Chinese, 6 Indian and 4 of other racial origins. Twenty-seven (52.9%) were HPV positive. Twenty-four (88.9%) had single infections (17 HPV18, 4 HPV16, 1 HPV45, 1 HPV68 and 1 positive for LIORF) and 3 double infections (2 HPV16+18 and 1 HPV18+59). As in most studies, HPV18 (74.1%) was the most frequently encountered followed by HPV16 (22.2%) and HPV45 and HPV 68 at 3.7% each.

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.

Conservative Treatment of Uterine Cervical Adenocarcinoma in Pregnancy

Cancer of the cervix is the most common malignancy diagnosed during pregnancy, with an incidence of 1–10 cases per 10,000 pregnancies. The desire of patients to maintain pregnancy and subsequent fertility is a difficult target to be achieved and should be widely studied, since it depends on the stage of disease, gestational age at diagnosis, and the woman's desire to maintain pregnancy. We describe in this report the case of a pregnant woman with invasive cervical adenocarcinoma in stage IB1 (FIGO) initially treated with neoadjuvant chemotherapy, followed by radical surgery and cesarean section in the same surgical procedure.

18F-FDG PET/CT Imaging of Sister Mary Joseph's Nodule

An 82-year-old woman was followed up for an uterine cervical adenocarcinoma treated by surgery. A whole-body fluorodeoxyglucose positron emission tomography study revealed a pathologic fluorodeoxyglucose uptake located in the umbilicus associated to peritoneal carcinomatosis. Biopsy of the umbilical nodule demonstrated an umbilical metastasis from the uterine adenocarcinoma, the so-called "Sister Mary Joseph's nodule."

Solitary cerebellous metastasis after prolonged remission in a case of uterine cervical adenocarcinoma

Intracranial metastasis of a uterine cervical carcinoma is a very rare occurrence. These metastases are characteristically multiple, supra-tentorial, associated with multiple systemic dissemination, usually occur relatively late in the course of the disease, and are most often seen in squamous carcinomas. We present an unusual case which defied these characteristics. This patient was in long-term remission (11 years), presented with a solitary cerebellous metastases, had no evidence of other systemic spread, and the pathology was an adenocarcinoma. We present this rare case with interesting clinical ramifications. This is probably the longest duration of remission prior to the metastasis in the published literature.

The Relationship Between ERCC1 Expression and Clinical Outcome in Patients With FIGO Stage I to Stage II Uterine Cervical Adenocarcinoma

Several studies have suggested that excision repair cross-complementation group 1 (ERCC1), a protein involved in nucleotide excision repair, is associated with resistance to platinum agent-based chemotherapy or chemoradiotherapy with platinum agents in various types of cancer. Herein we evaluated ERCC1 protein expression in uterine cervical adenocarcinoma and the relationship between this expression, clinicopathological factors, and clinical outcome, particularly in patients receiving adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. Thirty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to stage IIB cervical adenocarcinoma who underwent radical hysterectomy were evaluated. Excision repair cross-complementation group 1 protein expression was examined by immunohistochemistry in tumor tissues. The relationship between ERCC1 expression levels and clinicopathological factors (age, FIGO stage, histological grade, tumor size, vascular invasion, cervical stromal invasion, and lymph node metastases) and prognosis was evaluated. No significant differences between ERCC1 expression levels and clinicopathological factors were observed. The patients in the ERCC1 high-expression group (n = 7) experienced significantly worse disease-free survival than the patients in the ERCC1 low-expression group (n = 29; P = 0.005). Among the 25 patients who received cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, those with high ERCC1 expression (n = 5) also experienced significantly worse disease-free survival than those with low ERCC1 expression (n = 20; P = 0.002). Moreover, univariate and multivariate analyses revealed that high ERCC1 expression was an independent prognostic factor in patients receiving cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. This is the first analysis of the association between ERCC1 expression and clinical outcomes in patients with uterine cervical adenocarcinoma. High ERCC1 protein expression was revealed to be associated with worse disease-free survival in the patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin and was shown to be an independent prognostic factor. Further evaluation with a larger number of patients is required to confirm these preliminary observations.

Analysis of locally advanced uterine cervical adenocarcinoma treated with initial radiation therapy

Analysis of locally advanced uterine cervical adenocarcinoma treated with initial radiation therapy

LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix

Background. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. Materials and methods. LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. Results. In early-stage squamous cell carcinoma (stages IB–IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07–0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09–0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. Discussion and conclusion. LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.

Carcinomatous meningitis from adenocarcinoma of the uterine cervix: A case report and literature review

Carcinomatous meningitis from uterine cervix-related malignancies is a rare complication. We found only eight cases of meningeal metastasis from primary cervical carcinoma in the English-language medical literature. However, its incidence has increased recently, probably because carcinomatous meningitis is being identified more often and survival time for the primary disease is extended. Thus, the clinical signs and methods for diagnosis are of great importance. A 47-year-old Japanese woman had a stage IIIb uterine cervical adenocarcinoma. She chose initial chemotherapy followed by radical hysterectomy and adjuvant chemotherapy. Ten months after initial chemotherapy and 6 weeks after the last chemotherapy, she suddenly presented with unexplained neurological signs. We performed a lumbar puncture, which demonstrated adenocarcinoma cells compatible with metastases from the primary cervical adenocarcinoma. She died 7 weeks later. This rare complication occurs in the advanced stage of cervical cancer. Lumbar punctures for neoplastic cells are advised, and the prognosis remains poor.

Distinct DNA Methylation Profiles Between Adenocarcinoma and Squamous Cell Carcinoma of Human Uterine Cervix

Alterations in DNA methylation offer unique prospects as tumor markers. The big limitation in cervical cancer research is that it is too hard to obtain the pure normal tissue from a cervical cancer mass. So, we first profile type-specific DNA methylation of major two types of human uterine cervical cancer, adenocarcinoma (ACA) and squamous cell carcinoma (SCC), to establish a precise source of marker research. To assess the DNA methylation status of promoter regions in human uterine cervical ACAs and SCCs, fresh frozen tissues were obtained from bulky tumor masses to minimize the contamination from normal tissues and two array platforms using digestion with methylation-sensitive restriction-enzyme HpaII, ligation, and PCR were performed: an array of 11,994 (approximately 1.5 kb) PCR products from 10,445 promoter regions, and an array of 355,264 oligonucleotides for 18,212 HpaII fragments in 12,617 promoter regions. Loci near 21 genes showed significant differences between six ACA and four SCC from the analysis of two array data. Real-time PCR-based validation was performed on 13 loci using other nearby candidate methylation targets in the same promoter. Methylation patterns of 11 of 13 linked loci concurred with the microarray results. Four loci were further studied using tissues from additional patients (23 ACA and 24 SCC). Hypermethylation of loci in PAK6 and NOGOR most strongly correlated with ACA. Therefore, we have identified the 21 genes with differential methylation pattern between ACA and SCC and, furthermore, we found that PAK6 and NOGOR could be useful markers of ACA to be distinct from SCC.

A tumor of an ectopic ureter mimicking uterine cervix adenocarcinoma: case report and brief review

Single system ectopic ureter is a rare congenital malformation of the urinary tract, frequently associated with genital tract malformations. We report the first case of an adenocarcinoma arising in an ectopic ureter in a woman and mimicking uterine cervical adenocarcinoma. A 34-year-old woman, previously diagnosed as having bicornuate uterus, presented with post-coital bleeding. On gynecological exam, there were two cervixes with a small nodule on the left cervix. After nodule biopsy, the initial diagnosis was adenocarcinoma of the uterine cervix. Pelvic ultrasound and magnetic resonance imaging demonstrated an ectopic tumoral ureter draining a dysplastic pelvic kidney and inserted in the cervix of a bicornuate uterus. The patient was treated by radical hysterectomy and left nephroureterectomy. Pathological exam demonstrated an adenocarcinoma arising in the ectopic ureter. We suggest that this case could be an argument for recommending regular follow-up for women with ectopic ureter for detecting malignant transformation.

Detection and genotyping of human papillomavirus in biopsies of uterine cervical adenocarcinoma

The genotyping of Human Papillomavirus (HPV) will improve knowledge about the local epidemiological association of this virus with adenocarcinoma. To determine the frequency of HPV genotypes in biopsies of women with uterine cervical adenocarcinoma in a geographic region of Chile. Forty-one cervical biopsies with a pathological diagnosis of adenocarcinoma, corresponding to all women diagnosed with this cancer between 2002 and 2004, were analyzed. Viral gene Ll was amplified by PCRfor viral detection. HPV genotyping was carried out by a Reverse Line Blot technique. Seventy one percent of biopsies were positive for HPV. The most common genotypes found were HPV 16 (61%), followed by HPV 18 (19.5%). Eighty seven percent of biopsies had a single HPV infection. Three patients had a multiple HPV infection. All of the latter were infected by HPV 16, associated with other three viral genotypes (45, 52 and 66). No low-risk HPV genotypes were found. In this sample of biopsies, there was a high prevelence of HPV 16 and a low prevalence of HPV 18, which historically has been related to adenocarcinoma. The genotypes found correspond to those described in South America.

Detección y tipificación de virus papiloma humano en adenocarcinoma de cuello uterino mediante reverse line blot, Región de La Araucanía, Chile

The genotyping of Human Papillomavirus (HPV) will improve knowledge about the local epidemiological association of this virus with adenocarcinoma.To determine the frequency of HPV genotypes in biopsies of women with uterine cervical adenocarcinoma in a geographic region of Chile.Forty-one cervical biopsies with a pathological diagnosis of adenocarcinoma, corresponding to all women diagnosed with this cancer between 2002 and 2004, were analyzed. Viral gene Ll was amplified by PCRfor viral detection. HPV genotyping was carried out by a Reverse Line Blot technique.Seventy one percent of biopsies were positive for HPV. The most common genotypes found were HPV 16 (61%), followed by HPV 18 (19.5%). Eighty seven percent of biopsies had a single HPV infection. Three patients had a multiple HPV infection. All of the latter were infected by HPV 16, associated with other three viral genotypes (45, 52 and 66). No low-risk HPV genotypes were found.In this sample of biopsies, there was a high prevelence of HPV 16 and a low prevalence of HPV 18, which historically has been related to adenocarcinoma. The genotypes found correspond to those described in South America.