Tumor-infiltration of T-lymphocytes is inversely correlated with clinicopathologic factors in endometrial adenocarcinoma

OBJECTIVE: The aim of this study was to determine the distribution of T-lymphocytes and their relationship with clinicopathologic factors in endometrial carcinoma. METHODS: Samples were collected from 89 patients with endometrial endometrioid adenocarcinoma treated in Pusan National University Hospital from 2004 to 2011. Normal endometrial tissues were obtained from 30 hysterectomized women with benign adnexal masses and served as controls. Paraffin-embedded sections were immunohistochemically stained for CD8 (cytotoxic) and CD4 (helper) T-lymphocytes. The relationship of these cells with stage, histological grade, myometrial invasion, and lymph node metastasis was analyzed. RESULTS: The proportion of CD8+ and CD4+ lymphocytes in the endometrial endometrioid adenocarcinoma tissues was 67.4% (60/89) and 44.9% (40/89), respectively, which was significantly higher (P<0.05) than in the control group. The extent of CD8+ lymphocyte expression was negatively correlated with histologic grade, myometrial invasion, and lymph node metastasis. The proportion of infiltration of the CD4+ lymphocytes was negatively correlated with histologic grade and myometrial invasion. CONCLUSION: The high rate of infiltration of T-lymphocytes was negatively correlated with histologic grade, myometrial invasion, and lymph node metastasis. Our findings suggest that tumor-infiltrating T-lymphocytes may be used as pathologic prognostic factors in endometrial carcinoma.

The Role of TWIST in Ovarian Epithelial Cancers

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway. METHODS: We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1alpha (HIF1alpha), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters. RESULTS: The expression of TWIST, E-cadherin, HIF1alpha, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1alpha expression and reduced E-cadherin expression. The altered HIF1alpha/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS. CONCLUSIONS: Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1alpha/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

S100 expression in dendritic cells is inversely correlated with tumor grade in endometrial carcinoma

OBJECTIVE: The aim of this study was to determine the expression of S100 positive dendritic cells (DCs) and the relationship with clinicopathologic factors in endometrial carcinoma. METHODS: Samples were collected from 89 patients with endometrial endometrioid adenocarcinoma treated in Pusan National University Hospital from 2004 to 2011. Normal endometrial tissues were obtained from 30 hysterectomized women with benign adnexal masses and served as controls. Paraffin-embedded sections were immunohistochemically stained for S100 was performed, and the number of positive DCs was counted. The relationship of these cells to the stage, histological grade, myometrial invasion, and lymph node metastasis was analyzed. RESULTS: The proportion of S100-positive DCs in the endometrial endometrioid adenocarcinoma was 31.5% (28/89), which was significantly higher (P<0.05) than in the control group. The proportion of S100-positive DC expression was negatively correlated with the histologic grade, but was not associated with the stage, myometrial invasion, or lymph node metastasis. CONCLUSION: High DC density was inversely correlated with histologic grade in endometrial carcinoma. Tumor-infiltrating S100+ DCs may be used as pathologic marker in endometrial carcinoma.

Clinicopathological significance of atypical glandular cells on Pap smear

OBJECTIVE: To investigate the clinical significance of atypical glandular cells (AGC) by analyzing the prevalence and histologic outcomes of patients with AGC according to Pap smear. METHODS: The medical records of 83 patients who were diagnosed AGC on Pap tests at the Pusan National University Hospital outpatient department and health care center from January 1998 to March 2006 were reviewed. RESULTS: The prevalence of AGC was 55 of 54,160 (0.10%) and 28 of 54,160 (0.05%) for AGC-not otherwise specified (NOS) and neoplastic associated AGC, respectively. The histopathologic results of the AGC-NOS group (n=55) were as follows: low-grade squamous intraepithelial lesion, 7 (12.7%); high-grade squamous intraepithelial lesion, 4 (7.2%); adenocarcinoma of cervix, 3 (5.4%); endometrial carcinoma, 2 (3.6%); and other malignancies including 2 ovarian cancer cases and 1 breast cancer case, 3 (5.4%). The histopathologic results for the AGC-associated neoplastic group (n=28) were as follows: low-grade squamous intraepithelial lesion, 1 (3.5%); high-grade squamous intraepithelial lesion, 3 (10.7%); adenocarcinoma of cervix, 5 (17.8%); endometrial carcinoma, 4 (4.8%); and additional malignancies including 3 stomach cancer cases, 2 ovarian cancer cases, and 2 breast cancer cases; 7 (25%). CONCLUSION: AGCs may represent a variety of benign and malignant lesions. AGC-associated neoplastic findings may be related to gynecological or extrauterine malignancies. Thus, when AGCs, especially neoplastic AGCs, are encountered, it is best to evaluate the cervix not only for typical maladies, but also for gynecological and non-gynecological malignancies.

Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1alpha from human mesenchymal stem cells

Lysophosphatidic acid (LPA) stimulates growth and invasion of ovarian cancer cells and tumor angiogenesis. Cancer-derived LPA induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to alpha-smooth muscle actin (alpha-SMA)-positive cancer-associated fibroblasts. Presently, we explored whether cancer-derived LPA regulates secretion of pro-angiogenic factors from hASCs. Conditioned medium (CM) from the OVCAR-3 and SKOV3 ovarian cancer cell lines stimulated secretion angiogenic factors such as stromal-derived factor-1alpha (SDF-1alpha) and VEGF from hASCs. Pretreatment with the LPA receptor inhibitor Ki16425 or short hairpin RNA lentiviral silencing of the LPA1 receptor abrogated the cancer CM-stimulated expression of alpha-SMA, SDF-1, and VEGF from hASCs. LPA induced expression of myocardin and myocardin-related transcription factor-A, transcription factors involved in smooth muscle differentiation, in hASCs. siRNA-mediated depletion of endogenous myocardin and MRTF-A abrogated the expression of alpha-SMA, but not SDF-1 and VEGF. LPA activated RhoA in hASCs and pretreatment with the Rho kinase inhibitor Y27632 completely abrogated the LPA-induced expression of alpha-SMA, SDF-1, and VEGF in hASCs. Moreover, LPA-induced alpha-SMA expression was abrogated by treatment with the ERK inhibitor U0126 or the phosphoinositide-3-kinase inhibitor LY294002, but not the PLC inhibitor U73122. LPA-induced VEGF secretion was inhibited by LY294002, whereas LPA-induced SDF-1 secretion was markedly attenuated by U0126, U73122, and LY294002. These results suggest that cancer-secreted LPA induces differentiation of hASCs to cancer-associated fibroblasts through multiple signaling pathways involving Rho kinase, ERK, PLC, and phosphoinositide-3-kinase.

Comparison of the Usefulness of four Risk-of-Malignancy Indices using Ultrasonography in Ovarian masses

PURPOSE: The aim of this study was to evaluate the usefulness of four Risk-of-Malignancy Indices (RMI) in women with ovarian masses. MATERIALS AND METHODS: Between January 2007 and December 2008, 344 women who visited our hospital for surgical exploration due to an ovarian mass were enrolled in this study. Each RMI was based on the combination of menopausal status, ultrasound findings of ovarian masses, and absolute level of serum CA-125. A cutoff level of 200 was chosen as the threshold for determining between malignant and benign ovarian masses in RMI 1, RMI 2, and RMI 3. A cutoff level of 450 was chosen as the threshold in RMI 4. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: The combination of four malignancy indices is more accurate than menopausal status, ultrasound findings, and serum CA-125 alone, respectively for determining whether a mass is benign or malignant. RMI 1 and RMI 4 were found to be better than RMI 2 and RMI 3. RMI 4 was the most reliable test among them. The relationship between RMI 1 and RMI 4 was not statistically significant. With the cutoff level for RMI 4 at 450, the corresponding, sensitivity, specificity, positive predictive value, and negative predictive value were 72.1%, 88.0%, 56.4%, 93.9%, respectively. CONCLUSION: All four RMI were reliable tests for determining whether ovarian masses are malignant or benign, and RMI 4 was the most reliable index among them.

MyD88 expression and anti-apoptotic signals of paclitaxel in epithelial ovarian cancer cells / 대한산부인과학회지

OBJECTIVE: The objectives of this study was to evaluate the correlation between myeloid differentiation protein 88 (MyD88) expression and paclitaxel effects on epithelial ovarian cancer cells and to evaluate whether paclitaxel had anti-apoptotic signals. METHODS: Epithelial ovarian cancer cells isolated from ascites and established cell lines were treated with increasing concentrations of paclitaxel (0.2 to 20 microM) for 24 and 48 hours and cell viability was determined using the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. Nuclear factor-kappaB (NF-kappaB) activity was determined using a Luciferase reporter system. Levels of phospho-extracellular signal-regulated kinase (p-ERK) were measured by Western blot analysis. RESULTS: A strong signal for MyD88 expression was observed in R182, 01-19b and SKOV3 cells (MyD88-positive). A2780, R454 and 01-28 cells showed low levels of MyD88 (MyD88-negative). Paclitaxel effectively decreased cell viability in MyD88-negative A2780, R454, 01-28 cells after 24 and 48 hours (57%, 49%, 42% and 35%, 28%, 29%, respectively). MyD88-positive cells were resistant to paclitaxel. There was a significant increase in caspase-3/7 activity following paclitaxel treatment in MyD88-negative cells. No significant change in caspase-3/7 activity was detected in MyD88-positive cells. Paclitaxel induced NF-kappaB activation and enhanced the secretion of interleukin-6 (IL-6) and IL-8 in a dose dependent manner and induced ERK phosphorylation on MyD88-positive cells. CONCLUSION: Paclitaxel treatment for MyD88-positive ovarian cancer could have detrimental effects due to the paclitaxel-induced enhancement of NF-kappaB, ERK activities and pro-inflammatory cytokine production, which promote chemoresistance and tumor progression.

Anti-proliferative effect in epithelial ovarian cancer cells by MEK Inhibitor AZD6244 / 대한산부인과학회지

OBJECTIVE: The objectives of this study were to determine the efficacy of AZD6244, a potent, selective MEK inhibitor, in epithelial ovarian cancer (EOC) cells and to determine the enhanced cell death by combined treatment of paclitaxel and AZD6244. METHODS: EOC cells were treated with tenfold dilutions of AZD6244 (0.1 to 10 micrometer) for 24, 48 and 72 hours. Cell viability was determined by the CellTiter 96 AQueous One Solution Cell Proliferation Assay. The apoptotic cascade was assessed by Caspase-Glo assays. ERK activation was evaluated by Western blot analyses. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. RESULTS: In vitro cell viability showed that ovarian cancer cells with high p-ERK activities (A2780, R454, 01-28) exhibited significant growth inhibition. Cells with low p-ERK activities (R182, CP70), however, were resistant to AZD6244. Caspase-3 was not activated during AZD6244-induced growth inhibition. AZD6244 significantly inhibited p-ERK1/2 in both cell types regardless of constitutive levels of p-ERK. Proinflammatory cytokines including IL-6, IL-8, MCP-1 and GM-CSF were significantly decreased. Paclitaxel activated the p-ERK levels in paclitaxel-resistant R182 cells with low basal p-ERK level. MEK inhibition by AZD6244 enhanced paclitaxel-induced apoptosis significantly in R182 cells. CONCLUSION: These results demonstrate that AZD6244 has a potent growth inhibitory effect in ovarian cancer cells with high p-ERK activities. In addition, targeted inhibition of the extracellular signal-regulated kinase pathway with AZD6244 can enhance the anti-tumor efficacy of the cytotoxic paclitaxel.

The clinicopathological relationship of E2F-1 and Ki-67 expression in endometrial cancer / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate the correlation of E2F-1 and Ki-67 expression with clinicopathological prognostic factors. METHODS: Retrospectively, endometrial cancer slide samples (n=71) were analyzed. E2F-1 and Ki-67 were evaluated using immunohistochemical staining. And as a control (n=21), endometrial tissues were obtained by hysterectomy with benign gynecologic disease. RESULTS: Of 71 cases, the positive E2F-1 expression was 53.5% (38/71) in endometrial cancer. The expression of E2F-1 showed a remarkable positive correlation with myometrial invasion (P=0.001) and lymphovascular invasion (P=0.000). The Ki-67 labeling index was 30.56+/-25.67 in endometrial cancer and 9.38+/-8.35 in normal endometrial tissues (P=0.001). The Ki-67 labeling index showed positive correlations with increased tumor size (P=0.046, gamma=0.238), positive lymph node metastasis (P=0.001, gamma=0.396), cervical invasion (P=0.000, gamma=0.404) and lymphovascular tumor invasion (P=0.000, gamma=0.597). There was a positive correlation between E2F-1 and Ki-67 expression (P=0.000, gamma=0.734). CONCLUSION: The Ki-67 expression seems to be related with tumor invasiveness and growth in endometrial cancer and shows a remarkable positive correlation with E2F-1. The E2F-1 expression seems to be not related as a direct prognostic factor but related with tumor invasiveness and growth in endometrial cancer.

The clinicopathological relevance for the expression of cyclin E, CDK2, and p27 in endometrial carcinoma / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate the clinicopathological relevance for the expression of cyclin E, CDK2 and p27 in endometrial carcinoma. METHODS: With a retrospective review, slide samples (n=71) were analyzed. All patients had been treated with hysterectomy from January 1998 to December 2006. The expression of cyclin E, CDK2 and p27 were analyzed using immunohistochemical staining. RESULTS: Of 71 cases, the positive expression was cyclin E; 28 cases (39.4%), CDK2; 29 cases (40.8%). The expression of cyclin E showed positive correlation with lymph node metastasis (P=0.033) and estrogen receptor. The expression of CDK2 showed positive correlation with estrogen receptor (P=0.000). The negative expression of p27 was 42 cases (59.2%) and showed no correlation with other clinicopathological factors. Cyclin E overexpression with loss of p27 expression showed positive correlation with advanced stage (P=0.002), lymphovascular invasion (P=0.030) and lymph node metastasis (P=0.002). CONCLUSION: Cyclin E overexpression with loss of p27 expression could be an useful negative prognostic factors for endometrial carcinoma.

Rb pathway alteration and E2F-1 expression in epithelial ovarian cancer / 부인종양

OBJECTIVE: To evaluate the clinicopathological implications of Rb pathway alteration and E2F-1 expression in Epithelial ovarian cancer using immunohistochemical staining. METHODS: Tissue samples (n=72) were collected after staging operation between 1998 and 2004. RESULTS: In 72 cases, the overall expression of pRb, and E2F-1 were 59.7% (43/72), and 58.3% (42/72), respectively. pRb expression was inversely correlated with stage, histologic grade and mitotic index. E2F-1 expression was correlated with advanced stages, high grade, mitotic index, Ki-67 labeling index (LI). CONCLUSION: We suggest that Rb pathway alteration and E2F-1 expression could play roles as a new prognostic factors in Epithelial ovarian cancer.

The clinicopathological relevance of Poly (ADP-ribose) polymerase (PARP) expression in epithelial ovarian cancer / 대한산부인과학회지

OBJECTIVE: To evaluate the clinicopathological implication of poly (ADP-ribose) polymerase (PARP) expression in epithelial ovarian cancer. METHODS: Retrospectively, slide samples (n=72) were analyzed. PARP expression was analyzed using immunohistochemical staining. RESULTS: Of 72 cases, positive PARP expression were 27 cases (37.5%). PARP expression showed negative correlation with FIGO stage (p=0.004) and mitotic count (p=0.010), but showed no correlation with grade (p=0.053), tumor size (p=0.301), Ki-67 LIs (p=0.986), p53 positivity (p=0.414), and bcl-2 positivity (p=0.413). CONCLUSION: PARP expression showed negative correlation with advanced stage and mitoses in epithelial ovarian cancer. Therefore PARP expression could be a new prognostic factor in epithelial ovarian cancer.

MTA1 expression in epithelial ovarian neoplasm / 대한산부인과학회지

OBJECTIVE: MTA1 has been identified as a metastasis-promiting gene, and its gene expression is correlated with invasion and metastasis in several cancers. We examined MTA1 expression levels in epithelial ovarian neoplasm. METHODS: Expression of MTA1 was evaluated by immunohistochemistry and tissue array in 53 benign tumors, 27 borderline tumors and 68 malignant tumors. The data was analyzed in reference to various clinicopathological parameters. RESULTS: Increased expression of MTA1 was significantly correlated with histologic grade and FIGO stage. There was no relationship between MTA1 expression and age, histologic type, tumor size. CONCLUSION: These results suggest that MTA1 is closely related to invasiveness and progression in epithelial ovarian neoplasm. The MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.

A Case of Coincidental Gonadoblastoma and Dysgerminoma in 45X/47XYY Mosaic Turner Variant / 대한산부인과학회지

45X/47XYY mosaicism is a very rare sex chromosomal disorder with limited clinical information. We experienced an unusual mosaic syndrome in a 16-year old woman with a phenotypic female, short stature, and immature secondary sexual characteristics. We performed both gonadectomy and found a gonadoblastoma in one gonad and dysgerminoma in another gonad.

Radiosensitization by targeting radioresistance-related genes with protein kinase A inhibitor in radioresistant cancer cells

Here we determined which radiation-responsive genes were altered in radioresistant CEM/IR and FM3A/IR variants, which showed higher resistance to irradiation than parental human leukemia CEM and mouse mammary carcinoma FM3A cells, respectively and studied if radioresistance observed after radiotherapy could be restored by inhibition of protein kinase A. The expressions of DNA-PKcs, Ku70/80, Rad51 and Rad54 genes that related to DNA damage repair, and Bcl-2 and NF-kappaB genes that related to antiapoptosis, were up-regulated, but the expression of proapototic Bax gene was down-regulated in the radioresistant cells as compared to each parental counterpart. We also revealed that the combined treatment of radiation and the inhibitor of protein kinase A (PKA) to these radioresistant cells resulted in synergistic inhibition of DNA-PK, Rad51 and Bcl-2 expressions of the cells, and consequently restored radiosensitivity of the cells. Our results propose that combined treatment with radiotherapy and PKA inhibitor can be a novel therapeutic strategy to radioresistant cancers.

Factors related to postpartum weight retention / 대한산부인과학회지

OBJECTIVE: Pre-pregnancy weight and excess weight gain during pregnancy were associated with obstetric outcomes and plasma leptin was reported to have association with postpartum weight retention. The purpose of this study was to examine the relationships between pregnancy related factors including plasma leptin and weight gain during pregnancy and postpartum weight retention. METHODS: Seventy-five women were observed through pregnancy and 6 months postpartum. First trimester, third trimester and postpartum leptin were measured by radioimmunoassay. Weight gain categories were based on the Institute of Medicine recommendations. Relationships between pregnancy related factors and leptin were examined. And relationship between leptin and postpartum weight retention was also examined. RESULTS: Among subjects, 44.0% of women had concerns for postpartum weight retention and 18.9% had diet controls for postpartum weight management. Initial BMI categories by IOM classification were underweight, 29 (38.7%), normal, 37 (49.3%), and overweight group, 9 (12.0%). Underweight group was largely below IOM weight gain recommendation and overweight group was largely over IOM weight gain recommendation (P=0.013). First trimester leptin was correlated with pregravid BMI (r=0.678, P=0.000), maternal weight at term (r=0.547, P=0.006) and postpartum BMI (r=0.608, P=0.002), but not correlated with weight gain during pregnancy and postpartum weight retention. Third trimester leptin was not correlated with above variables. Initial BMI categories by IOM were significantly correlated with first trimester leptin, leptin at 5 weeks postpartum, maternal weight at term (0.741, P=0.000), weight at 5 weeks postpartum (r=0.728, P=0.001) and weight at 6 months postpartum (r=0.684, P=0.002). CONCLUSION: These results suggest that first trimester plasma leptin may predict maternal weight at term and initial BMI categories may be a predictor of maternal weight at 5 weeks postpartum and 6 months postpartum. However, weight gain during pregnancy was not correlated with postpartum weight retention.

A case of Gliomatosis Peritonei after 10 years following Operation of Immature Teratoma of the Ovary / 부인종양

Gliomatosis peritonei, the implantation of neuroglial tissue upon the peritoneal surface, is a rare event most often associated with solid or immature teratoma of the ovary in young girls. The majority of cases occur in association with teratomas containing immature element. However malignant transformation of the glial tissue has been reported. Here we experienced a case of mature glial implants presenting in an 27-year-old female, 10 years after initial diagnosis and removal of an ovarian immature teratoma, and report this case with brief review of literatures.

Follow-up of Cervical Intraepithelial Neoplasia after Conization: The Clinical Usefulness of Repeat Conization / 대한산부인과학회지

OBJECTIVE: This study is aimed to analyze the results of follow up after conization and to determine the value of repeat conization for treatment of cervical intraepithelial neoplasia (CIN) III. METHODS: Between March 1998 and February 2002, 241 women were underwent knife conization due to CIN III of the uterine cervix. After knife conization, follow-up visits were scheduled at 2 weeks interval during the first 3 months for cervical inspection only, then at every 3 months for the first year, every 6 months for the second year, and then annually for pelvic examination and Papanicolaou smears. Among 241 patients, 71 women were suspected of residual or recurrent lesions by cytology and colposcopy. Among 71 patients with residual or recurrent lesions, 37 patients received simple hysterectomy and 34 patients received repeat conization. RESULTS: The mean age of the patients was 36.4 years (range 27-64) and mean parity was 2 (range 0-6). The mean follow-up duration was 25.4 months (range 14-51) after conization. The results of repeat conization (n=34) were as follows; no residual lesion in 7 patients, CIN III in 15 patients, and lower grade neoplasia in 12 patients. Two patients were margin positive; 1 patient with CIN III, 1 patient with lower grade neoplasia. The outcomes of simple hysterectomy (n=37) were as follows; no residual lesion in 8 patients, CIN III in 18 patients, and lower grade neoplasia in 11 patients. Resection margin negative rates of repeat conization and simple hysterectomy were 94.1% and 100%, respectively (p>0.05). CONCLUSION: This study suggests that less invasive technique such as repeat conization might be an alternative method instead of hysterectomy in selected patients with recurrent or residual lesions who wish to preserve fertility.

Analysis of MTA1 gene expression for uterine cervical cancer by cDNA microarray and tissue array / 대한산부인과학회지

OBJECTIVE: cDNA microarray and tissue array was utilized for the profiling of differentially expressed genes in uterine cervical squamous cell carcinoma. Metastasis associated 1 gene (MTA1) was investigated using these methods, and we correlated gene and protein expression of MTA1 with the invasion and metastasis of cancer. METHODS: Gene expression profiles for paired cancerous and noncancerous uterine cervical tissue samples from an individual by means of a cDNA microarray representing 17,000 genes were analyzed. Of the differentially expressed genes, we assessed the MTA1 gene at the protein level using tissue array and immunohistochemistry. RESULTS: The expressions of 15 and 21 genes were noted to have more than fivefold increase or decrease in the cervical squamous cell carcinoma tissue compared to the non-cancerous cervical tissue. The changed genes were those associated with DNA synthesis/repair, apoptosis, modulation of transcription, signal transduction, enzyme, cell cycle, cytoskeleton, metabolism, cell adhesion, extracellular matrix, immune response and others. Expression of MTA1 was evaluated by immunohistochemistry in 34 squamous cell carcinoma in situ, 32 microinvasive carcinoma and 56 invasive squamous cell carcinoma. Increased expression of MTA1 was significantly correlated with depth of invasion and lymph node metastasis. There was no statistically significant relationship between MTA1 expression and age, and FIGO stage. CONCLUSION: These results suggest that MTA1 may closely related to invasiveness and progression in cervical cancer. Thus, MTA1 could potentially provide information on the mechanism of cancer invasion and metastasis.

Relationship between the Expression of COX-1, COX-2, p53 and VEGF and Prognostic factors in Squamous cell carcinoma of Uterine cervix / 대한산부인과학회지

OBJECTIVE: The aim of this study was to examine that COX-1, COX-2, p53 and VEGF expression are associated with prognostically worse pathological variables and to investigate whether the enhanced COX-2, tumor microvessel density and VEGF expression is showed in invasive cervical cancer. METHODS: From January 1998 to December 2001, sixty-three cases of paraffin-embedded cervical specimens were obtained by surgical resection in the Pusan National University Hospital. All tissues were subjected to immunohistochemical staining for COX-1, COX-2, p53, VEGF and microvessel density. Clinical factors such as age, FIGO stage and pelvic lymph node metastasis were evaluated. RESULTS: In COX-1 expression, no staining and cells staining positive less than 10% were 49, 13 cases, respectively. In contrast, COX-2 expressions was demonstrated in the cells staining positive 10% to 50% and greater than 50% were 25, 17 cases, respectively. The positivities of p53 and VEGF were 68.3% (43/63), 77.8% (49/63), respectively. There was a significant correlation between COX-2 and VEGF expression (p<0.05) in cervical cancer. Also the relationship existed between VEGF and microvessel count. But there was no correlation between COX-2, microvessel count and clinicopathologic factors in cervical cancer. CONCLUSION: These findings provide evidence that the expression of COX-2 and VEGF may be involved in the promotion of angiogenesis in cervical cancer.