Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer.

Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients' plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively. Moreover, the accuracy was good enough for MEG3 methylation in plasma to discriminate CIN III patients from healthy participants. In addition, MEG3 methylation in plasma also has high discriminating power to predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation of MEG3 in plasma was associated with worse recurrence-free and overall survival in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve as a diagnostic and prognostic biomarker for cervical cancer, providing useful information for clinical management.

Hyaluronic acid binding protein 1 overexpression is an indicator for disease-free survival in cervical cancer.

BACKGOUND: Hyaluronic acid binding protein 1 (HABP1) is reported to overexpress in various cancer tissues and may therefore contribute to oncogenesis. However, the status of HABP1 expression in cervical cancer (CC) remains unknown. The aim of this study was to investigate the role of HABP1 and its relationship with clinical characteristics in patients with CC. METHODS: Immunohistochemistry was used to explore the expression of HABP1 in 30 cervical intra-epithelial neoplasia (CIN) and 118 CC specimens compared to 10 normal cervical specimens. RESULTS: HABP1 expression was found to be positively higher in CC than in CIN2/3 cases (P = 0.020). Moreover, clinicopathological analysis showed that HABP1 overexpression was associated with advanced FIGO stage (P = 0.001), poor histologic grade (P = 0.013), large tumor size (P = 0.025), LVSI (P = 0.024), deep stromal infiltration (P = 0.001), and lymph node metastasis (P = 0.023). Multivariate analysis suggested that HABP1 overexpression was an independent factor for disease-free survival (DFS) (hazard ratio 3.082; 95% confidence interval 1.372-7.501; P = 0.007). CONCLUSIONS: The present data provide evidence that HABP1 overexpression predicts CC with high-risk factors and may therefore serve as a new molecular marker for the prediction of DFS in these patients.

High-mobility group box 1 is overexpressed in cervical carcinoma and promotes cell invasion and migration in vitro.

The present study aimed to investigate the expression of high-mobility group box 1 protein (HMGB1) in cervical carcinoma and explore whether or not HMGB1 promotes cervical carcinoma cell invasion and migration in vitro and the related mechanism. HMGB1, nuclear factor-κB (NF-κB), E-cadherin and N-cadherin protein expression was analyzed in tissues from 48 cervical carcinomas, 51 cervical intraepithelial neoplasia (CIN) and tissues from 24 healthy controls using immunohistochemistry. HeLa cells were treated with different concentrations of HMGB1 (0, 10, 100, and 1,000 ng/ml) at different time-points (0, 24, 48 and 72 h), and changes in cell morphology and biological behaviors were observed. Changes in the expression levels of E-cadherin, N-cadherin, NF-κB and the inhibitor κB (IκB) in the treated cells were detected by western blot analysis and real-time PCR. HMGB1 expression exhibited a gradually increasing trend in the normal cervical tissues, CIN and cervical cancer, and there was statistical significance between the three groups (P<0.05). HMGB1 expression level was associated with FIGO stage, lymph node metastasis and differentiation (P<0.05). HMGB1 expression was positively related to N-cadherin and NF-κB; and HMGB1 had a negative relationship with E-cadherin. HMGB1 stimulation caused HeLa cells to lose cell polarity and transition from epithelial cells into spindle-shaped cells with sparse cell-cell junctions. The expression levels of E-cadherin and IκB in the cytoplasm were reduced, while N-cadherin expression was increased. The level of NF-κB expression in the nucleus was also increased. Treatment with NF-κB inhibitor (BAY11-7082) and receptor for advanced glycation end products (RAGE) antagonist (anti-RAGE) significantly suppressed HMGB1­mediated epithelial-to-mesenchymal transition in the HeLa cervical cancer cells. The results suggest that HMGB1 is associated with outcomes of cervical cancer and promotes subsequent invasion and metastasis of cervical cancer cells by activating the NF-κB signaling pathway. This potential mechanism could be an important determinant of cervical cancer metastasis.

Invasive Stratified Mucin-producing Carcinoma and Stratified Mucin-producing Intraepithelial Lesion (SMILE): 15 Cases Presenting a Spectrum of Cervical Neoplasia With Description of a Distinctive Variant of Invasive Adenocarcinoma.

Stratified mucin-producing intraepithelial lesion (SMILE) is a cervical intraepithelial lesion, distinct from conventional squamous or glandular counterparts, believed to arise from embryonic cells at the transformation zone by transdifferentiation during high-risk HPV-associated carcinogenesis. It is characterized by stratified, immature epithelial cells displaying varying quantities of intracytoplasmic mucin throughout the majority of the lesional epithelium. We identified a distinct form of invasive cervical carcinoma with morphologic features identical to those in SMILE, which we have termed "invasive stratified mucin-producing carcinoma." Fifteen cases from 15 patients (mean 36 y; range, 22 to 64 y) were retrieved from the pathology archives of multiple institutions with a diagnosis of either SMILE or invasive cervical carcinoma with a description or comment about the invasive tumor's resemblance to SMILE. Seven cases had solely intraepithelial disease with a component of SMILE (mean 29 y; range, 22 to 40 y). The 8 other cases had invasive stratified mucin-producing carcinoma (mean 44; range, 34 to 64 y) in which SMILE was identified in 7. All cases of invasive stratified mucin-producing carcinoma demonstrated stratified, immature nuclei with intracytoplasmic mucin, which morphologically varied between cases from "mucin-rich" to "mucin-poor" in a similar manner to SMILE. All cases had mitotic figures and apoptotic debris, and an intralesional neutrophilic infiltrate was seen in the majority of cases. In cases of invasive carcinoma, the depth of invasion ranged from <1 to 19 mm. Follow-up information was available in 8 cases and ranged from 1 to 36 months (mean 11 mo). Three cases of invasive stratified mucin-producing carcinoma had biopsy or resection-proven metastatic carcinoma on follow-up. These 15 cases of cervical stratified mucin-producing lesions show a combination of intraepithelial and invasive growth patterns. Given that SMILE is well rooted as a distinct intraepithelial lesion, we propose "invasive stratified mucin-producing carcinoma" to describe its corresponding form of invasive carcinoma.

Astrocyte elevated gene-1 promotes progression of cervical squamous cell carcinoma by inducing epithelial-mesenchymal transition via Wnt signaling.

OBJECTIVE: The aim of this study was to investigate the association of astrocyte elevated gene-1 (AEG-1) with epithelial-mesenchymal transition of cervical squamous cell carcinoma (CSCC) and the underlying mechanisms. METHODS: The expression of proteins was determined by immunohistochemistry in tissues. Overexpression and knockdown of AEG-1 in SiHa cells were achieved by stable AEG-1 gene transfection (SiHa-AEG-1+) and AEG-1-siRNA (SiHa-AEG-1-), respectively. The cellular levels of messenger RNA and proteins were assessed with reverse transcription polymerase chain reaction and Western blotting, respectively. The cell invasion capacity was assessed by the chamber invasion assay. RESULTS: AEG-1 was overexpressed in clinical CSCC and associated with lymph node metastasis, parametrial involvement, stromal invasion, and vascular invasion. A high level of vimentin and a low level of E-cadherin were also detected in the cancer tissues. AEG-1 expression was positively correlated with vimentin expression and negatively with E-cadherin expression in CSCC tissues. In addition, high level of AEG-1 was related to unfavorable prognosis of CSCC. On a cellular level, overexpression of AEG-1 was found to lead to an up-regulation of vimentin and a down-regulation of E-cadherin on messenger RNA and protein level in SiHa cells, whereas AEG-1 knockdown led to a contrary result. Meanwhile, the nuclear levels of NF-κB p65 and ß-catenin were also increased in SiHa-AEG-1+, whereas their nuclear levels were decreased in SiHa-AEG-1-. Inhibition of Wnt signaling significantly reduced vimentin level and enhanced E-cadherin level in SiHa-AEG+, but inhibition of NF-κB signaling did not. SiHa-AEG-1+ and SiHa-AEG- showed an enhanced and a decreased invasive capacity, respectively. The enhanced invasiveness of SiHa-AEG-1+ was weakened by inhibition of Wnt signaling. CONCLUSIONS: AEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.

Role of CXCR7 and effects on CXCL12 in SiHa cells and upregulation in cervical squamous cell carcinomas in Uighur women.

CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the function and molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present study a loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interfering RNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, as indicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chain reaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with control cells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12 was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathological pattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients with CSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa, especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulated by CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis.

Clinical significance of Wnt-11 and squamous cell carcinoma antigen expression in cervical cancer.

The purpose of the study was to determine the expression patterns of Wnt-11 and squamous cell carcinoma antigen in cervical cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Wnt-11 and squamous cell carcinoma antigen was detected in 127 cervical cancer tissues, 21 cervical intraepithelial neoplasia, as well as in 20 healthy controls by immunohistochemistry, and the relationship of Wnt-11 and squamous cell carcinoma antigen expression with clinicopathological parameters was analyzed. Both Wnt-11 and squamous cell carcinoma antigen were more commonly expressed in cervical cancer than in cervical intraepithelial neoplasia and in normal cervical tissue (respectively; P < 0.05); further, Wnt-11 and squamous cell carcinoma antigen expression in cervical cancer were positively correlated (r = 0.271, P < 0.05). In comparing the expression with clinicopathological parameters of tumor samples, Wnt-11 and squamous cell carcinoma antigen were both associated with FIGO stage, lymph node metastasis, and tumor size (P < 0.05), but not with patient age, pathological type, or differentiation. Increased Wnt-11 protein levels in cervical carcinoma samples were associated with a poor outcome in univariate and multivariate analysis. Wnt-11 and squamous cell carcinoma antigen are related to the malignancy degree and metastasis of cervical cancer, and thus may play a coordinating role in the occurrence and progression of cervical cancer. The study indicated that Wnt-11 may be a useful prognostic indicator for cervical carcinoma.

Comportamiento del cáncer cérvicouterino en el municipio San Antonio del Sur de Guantánamo / Behavior of cervicouterine cancer in the San Antonio del Sur municipality, Guantanamo province

Introducción: no son pocos los esfuerzos que se realizan para combatir el cáncer cérvicouterino, a pesar de que existe un programa de detecci¾n precoz, estamos lejos aún de alcanzar la meta propuesta. Objetivo: conocer el comportamiento del cáncer cérvicouterino en el municipio de San Antonio del Sur de la provincia Guantánamo en el periodo 2006-2010. Métodos: el universo de estudio quedó constituido por las 254 pacientes que tuvieron una citología orgánica con diagnóstico positivo de lesiones premalignas o malignas de cuello uterino. Los datos se extrajeron de las tarjetas de citología de cada área de salud, se procesaron en hojas de cálculo de Microsoft Excel, se expresaron en números absolutos y porcientos y se representaron en tablas y gráficos...

Introduction: many efforts are made to fight against the cervicouterine cancer despite a program of early detection the goal is far from to be achieved yet. Objective: to know the behavior of cervicouterine cancer in the San Antonio del Sur municipality in the Guantánamo province during 2006-2010. Methods: the study universe included 254 patients with a organic cytology and positive diagnosis of premalignant or malignant lesions of cervix. Data were collected from the cytology cards of each health area, the calculus sheets of Microsoft Excel were processed, expressed in absolute figures and percentages represented in tables and charts...

Comportamiento del cáncer cérvicouterino en el municipio San Antonio del Sur de Guantánamo / Behavior of cervicouterine cancer in the San Antonio del Sur municipality, Guantanamo province

Introducción: no son pocos los esfuerzos que se realizan para combatir el cáncer cérvicouterino, a pesar de que existe un programa de detecci¾n precoz, estamos lejos aún de alcanzar la meta propuesta. Objetivo: conocer el comportamiento del cáncer cérvicouterino en el municipio de San Antonio del Sur de la provincia Guantánamo en el periodo 2006-2010. Métodos: el universo de estudio quedó constituido por las 254 pacientes que tuvieron una citología orgánica con diagnóstico positivo de lesiones premalignas o malignas de cuello uterino. Los datos se extrajeron de las tarjetas de citología de cada área de salud, se procesaron en hojas de cálculo de Microsoft Excel, se expresaron en números absolutos y porcientos y se representaron en tablas y gráficos...

Introduction: many efforts are made to fight against the cervicouterine cancer despite a program of early detection the goal is far from to be achieved yet. Objective: to know the behavior of cervicouterine cancer in the San Antonio del Sur municipality in the Guantánamo province during 2006-2010. Methods: the study universe included 254 patients with a organic cytology and positive diagnosis of premalignant or malignant lesions of cervix. Data were collected from the cytology cards of each health area, the calculus sheets of Microsoft Excel were processed, expressed in absolute figures and percentages represented in tables and charts...

Over-expression of protein kinase C isoforms (α, δ, θ and ζ) in squamous cervical cancer.

Protein kinase C was found to be significantly over-expressed in cancer samples compared to adjacent normal cervical tissues by proteomics in our previous study. The aim of this study was to examine protein kinase C expression and to analyze the expression patterns of protein kinase C isoforms in squamous cervical cancer at the protein levels and their associations with clinical and pathologic factors of squamous cervical cancer. First, Western blotting was used to examine protein kinase C expression in the specimens of tumors and matched adjacent normal tissues which were collected from 12 patients with squamous cervical cancer. Protein kinase C isoforms (α, δ, θ and ζ) expression were then detected by immunohistochemistry in other 43 cases of squamous cervical cancer tissues, 32 cases of corresponding adjacent normal cervical squamous epithelial tissue and 31 cases of cervical intraepithelial neoplasia. Western blot analysis revealed that protein kinase C expression was positive in squamous cervical cancer while it was not expressed in normal cervical tissues. On the other hand, immunohistochemical analysis suggested that, protein kinase C isoforms (α, δ, θ and ζ) expression was significantly higher in squamous cervical cancer compared to cervical intraepithelial neoplasia, as well as in cervical intraepithelial neoplasia compared with normal tissues, respectively.High levels of protein kinase C α expression were associated with cellular differentiation(P<0.05). Protein kinase C δ was significantly associated with tumor stage (P<0.05) and protein kinase C ζ was associated with lymphatic metastasis (P < 0.05). These findings indicate that protein kinase C isoforms expression in cervical lesions was associated with carcinogenesis and might play important roles throughout the process of cervical cancer development.

Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade.

BACKGROUND: The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. METHODS: In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. RESULTS: On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. CONCLUSIONS: These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

Immunolabeling of the inhibin-ßA and -ßB subunit in normal and malignant human cervical tissue and cervical cancer cell lines.

OBJECTIVES: Inhibins, dimeric peptide hormones composed of an α-subunit and 1 of 2 possible ß subunits (ßA or ßB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. However, it is still unclear whether normal and cancerous cervical tissues as well as cervical cancer cell lines express the inhibin-ßA and -ßB subunits. MATERIALS AND METHODS: Normal human uterine cervical tissue was obtained from 4 premenopausal nonpregnant patients. In addition, a total of 32 specimens of cervical intraepithelial neoplasia (CIN) of different stages were obtained (CIN 1 = 10, CIN 2 = 9, and CIN 3 = 13). Moreover, 30 squamous cervical cancer samples of well-differentiated (grade 1; n = 10), moderate differentiated (grade 2; n = 10), and poorly differentiated (grade 3; n = 10) grading were analyzed. RESULTS: An immunohistochemical staining reaction for inhibin-ßA and -ßB subunits could be observed in normal and malignant cervical tissue as well as in cervical cancer cell lines. Regarding inhibin-ßA significant differences were observed between normal tissue and CIN 1 and CIN 3. Moreover, the immunohistochemical staining reaction for inhibin-ßA was significantly higher in CIN 3 compared with that in cervical carcinoma grades 1 and 2. The inhibin-ßB expression was higher in CIN and cervical cancer compared with that in normal cervical tissue. Inhibin-ßB was significantly higher in CIN 2 and CIN 3 compared with cancer tissues of histological grade 1. In addition, a significant increase of the staining intensity was observed between cervical cancer grades 1 and 2 as well as grade 3. CONCLUSIONS: Both inhibin-ß subunits demonstrated a differential expression in CIN and squamous cancer, suggesting important roles in cervical carcinogenesis. Inhibin-ßA might be important during progression of CIN, whereas the inhibin-ßB subunit could exert a substantial function during differentiation of cervical carcinomas. Moreover, the synthesis of this subunit in cervical carcinoma cell lines also allows the use of this cell line to elucidates their functions in cervical cancer pathogenesis.

Systemic leukocyte alterations are associated with invasive uterine cervical cancer.

OBJECTIVE: The aim of the study was to evaluate blood leukocyte counts in patients with uterine cervical neoplasia. METHODS: Patients treated at a university hospital were reviewed retrospectively. Disease progression was monitored, beginning in 1990 to 2002, for at least 5 years. Blood count parameters included absolute leukocyte, neutrophil and lymphocyte counts, leukocytosis (white blood cells > 10³/µL), neutrophilia (neutrophils ≥ 70% of leukocytes), lymphopenia (lymphocytes ≤ 15% of leukocytes), and the neutrophil-lymphocyte ratio (NLR), categorized as less than 5 or 5 or greater. RESULTS: A total of 315 patients were enrolled: 182 (57.8%) with preinvasive neoplasia (cervical intraepithelial neoplasia [CIN] group), 95 (30.1%) with stages I to II (early group), and 38 patients (12.1%) with stages III to IV neoplasia (advanced group). Neutrophil and lymphocyte counts were elevated and reduced, respectively, at advanced stages compared with the CIN group (P < 0.05). Leukocytosis, neutrophilia, lymphopenia, and an NLR of 5 or greater were more frequent at advanced stages compared with the CIN and early-stage groups (P < 0.05). Moreover, neutrophilia was also significantly more frequent at early stage compared with the CIN group. The advanced group with neutrophilia had increased frequency of recidivism and metastasis than patients in the CIN group with neutrophilia (P < 0.05). CONCLUSIONS: Patients with advanced cervical cancer had significantly higher frequency of leukocyte alterations, although they may occur apart from the preinvasive stages. Overall, neutrophilia was the best indicator of cancer invasiveness.

Assessment of gynecologic malignancies: a multi-center study in Tehran (1995-2005).

OBJECTIVE: The observed differences in cancer incidence are mainly due to different individuals and social risk factors. This study aims to demonstrate the characteristics of female genital malignancies according to the pathological records in Tehran, Iran. MATERIALS AND METHODS: In this cross-sectional study, all records of pathological specimens categorized as ovarian, uterine corpus or uterine cervix cancers from 1995 to 2005, in five teaching hospitals in Tehran, were studied. Age, marriage, parity, menopausal status, smoking, oral contraceptive usage, pathological staging, and histological grading were reviewed by a trained general practitioner. SPSS 14 was used for statistical analysis. RESULT: Mean age (SD) at the time of diagnosis was 50 (15). Fifty-nine percent of ovarian, 33.9 and 47.7% of uterine corpus and uterine cervix malignant patients were premenopausal. About 90% of all were nonsmokers and 82.7% were multiparae. Various types of gynecologic malignancies included ovarian (55.5%), uterine corpus (24.9%), and uterine cervical cancers (19.6%) were diagnosed. In tumors of the uterine corpus and uterus cervix, the most frequent stage of diagnosis was stage IIA. CONCLUSION: Ovarian cancer was the most frequently occurring gynecologic tumor. Although distribution of age in ovarian cancer was similar to that mentioned in the literature, occurrence of the cancer was more frequent in the premenopausal state.

Human papillomavirus infection in patients with residual or recurrent cervical intraepithelial neoplasia.

AIMS AND BACKGROUND: The main purpose of this longitudinal study was to evaluate the frequency of HPV infection in patients with residual or recurrent CIN. METHODS: 797 consecutive patients with CIN, treated with conization, were included. In 38 patients with residual or recurrent CIN in whom reconization was performed, infection with high-risk HPV types was analyzed. RESULTS: Reconization was performed in 4.8% of patients. Before reconization, 21 patients (55.3%) were infected with high-risk HPV and 17 patients (44.7%) were HPV negative. Among the HPV-negative patients, two (11.8%) had CIN 1, five (29.4%) CIN 2, nine (52.9%) CIN 3 and one patient (5.9%) had microinvasive cancer of the uterine cervix. The difference in frequency of infection with high-risk HPV was not significant (chi-square 0.372; P > 0.05). CONCLUSIONS: On the basis of the study results it is not possible to recommend the HPV test as the only method of detection of residual or recurrent CIN after conization.

Groin metastasis after extensive microinvasive vulvar cancer. A case report.

BACKGROUND: An increasing incidence of vulvar intraepithelial neoplasia and microinvasive vulvar cancer is being observed in younger patients. The treatment of choice is wide local excision. CASE: A 53-year-old woman had HPV-related disease for more than 20 years. Following several operations for cervical and vulvar intraepithelial lesions (CIN 3 and VIN 3) and genital warts, she presented with extensive, multifocal VIN 3 and microinvasion at the age of 50. Since a radical approach was not feasible, combined excision and laser therapy was performed, preceded by mapping of the abnormal areas of the vulva. Two years after surgery the patient presented with a mass in the right groin. Histopathologic examination following excision revealed a groin metastasis. Postoperative radiotherapy was performed. Three years after the last vulvar surgery and 1 year after groin excision, the patient was well and disease free. CONCLUSION: In high-risk patients with recurrent HPV-related disease of the lower genital tract and extensive microinvasive vulvar carcinoma, removal of the groin nodes should be considered. The sentinel node approach might be appropriate in the future.

Syndecan-1 expression in cancer of the uterine cervix: association with lymph node metastasis.

The development of carcinoma is associated with alterations in the expression of many cell adhesion molecules. Syndecan-1 is a cell surface proteoglycan that binds cells to the extracellular matrix and changes its expression following malignant transformation in some tumors. Our purpose was to examine the pattern of syndecan-1 expression in cancer of the uterine cervix and assess the clinicopathological significance of syndecan-1 expression. A total of 106 tissue specimens (6 normal, 19 cervical intraepithelial neoplasia (CIN) and 81 invasive cancer) were analyzed immunohistochemically. In addition, the corresponding expression of mRNA in tumor tissues was evaluated by reverse transcription-polymerase chain reaction (RT/PCR) in comparison with normal counterparts. Syndecan-1 was positive in normal squamous cells except the basal cell layer. The intensity of syndecan-1 staining was the strongest in normal epithelium, followed by CIN, and invasive squamous cell carcinoma. Syndecan-1 expression in cancer tissue tended to be higher in keratinizing type than non-keratinizing type and not found in adenocarcinoma. Syndecan-1 expression was markedly decreased at the mRNA level in invasive squamous cell carcinoma as compared with that of normal uterine cervix. Interestingy, there was an inverse correlation between the expression of syndecan-1 in the primary site and lymph node metastasis, although there was no significant correlation between syndecan-1 expression and the prognosis. The results of the present study suggest that syndecan-1 expression is associated with squamous tissues and plays a key role in the progression of the cancer of the uterine cervix especially in the metastatic process.

Early invasive adenocarcinoma of the cervix.

BACKGROUND: Adenocarcinoma of the cervix is increasing in frequency. There is a dearth of specific detail concerning the histomorphology, histogenesis, and associated findings in early invasive cervical adenocarcinoma. METHODS: Forty cases of cervical adenocarcinoma invasive to 5 mm or less were examined in detail. RESULTS: Mean patient age was 40.9 years. In 78% of the cases, the midpoint of the invasive focus was in the region of the squamocolumnar junction or transformation zone; more than 1 invasive focus was present in 4 cases. Eighty-five percent of cases also had adenocarcinoma in situ (AIS). In 9 of 10 minimally invasive cases, small invasive glands were present in the stroma adjacent to AIS. In some of these, the AIS had preinvasive buds that were still attached. Endometrioid adenocarcinomas were associated with AIS but were located higher in the canal than the more common endocervical type. All three adenosquamous carcinomas were associated with both squamous intraepithelial neoplasia and AIS. Vascular space invasion was observed in two cases, microglandular hyperplasia in four. CONCLUSIONS: Adenocarcinoma in situ is the precursor to most adenocarcinomas of the cervix with an average interval between clinically detected AIS and early invasion of approximately 5 years, supporting the potential for Papanicolaou test screening to prevent this disease. However, the existence of small carcinomas in the absence of AIS suggests the possibility of rapid progression in some cases. Invasion occurs by budding from or expansion of AIS glands, usually in the region of the squamocolumnar junction. Multifocal invasion is uncommon, as is vascular invasion in early lesions. The endometrioid variant has the same histogenesis as the endocervical type but may arise higher in the canal. The precursor of adenosquamous carcinoma has a similar bimorphic differentiation potential. Microglandular hyperplasia is not related to early invasive adenocarcinoma.