Ha-Jeong Kim

Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: A meta-analysis

OBJECTIVE To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC). METHODS From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria. RESULTS Heterogeneity tests demonstrated significant between-study variation (I(2)=92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I+II, and stage III+IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I+II; HR; 1.17, 95% CI; 1.01-1.36, stage III+IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86). CONCLUSION This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.

Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer

Galectin 1 is a 14-kd laminin-binding lectin involved in important biologic mechanisms of tumors, including neoplastic transformation, cell survival, angiogenesis, cell proliferation, and metastasis. In this study, we investigated the role of galectin 1 in cell survival and metastasis in cervical cancer. The expression of galectin 1 was determined in 73 formalin-fixed, paraffin-embedded cervical cancer tissues using an immunohistochemical method and compared with clinicopathologic risk factors for recurrence after surgery. To evaluate the role of galectin 1 in cell proliferation and invasion, we performed proliferation and invasion assays with galectin 1 small interfering RNA (siRNA) using cervical cancer cell lines, including HeLa and SiHa cells. Immunohistochemical analysis revealed that galectin 1 expression was found in most peritumoral stroma samples (72/73; 98.6%). Galectin 1 expression was significantly correlated with the depth of invasion in the cervix (P=.015) and lymph node metastasis (P=.045) on univariate analysis. When progression-free survival of all of the patients studied was analyzed based upon galectin 1 expression, galectin 1 expression was not correlated with progression-free survival (P=.32). Down-regulation of galectin 1 using small interfering RNA resulted in the inhibition of cell growth and proliferation of HeLa and SiHa cells. Moreover, the ability of cells to invade was significantly reduced by galectin 1 small interfering RNA. Our results revealed that high galectin 1 expression in peritumoral stroma was significantly correlated with depth of invasion in cervical lesions and lymph node metastasis of cervical cancer and that galectin 1 may be functionally involved in cell proliferation and invasion.

High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion

PURPOSE Galectin-1 (Gal-1) is a 14-kDa laminin-binding galectin involved in several biological events including regulation of tumour proliferation and metastasis. In this study, we investigated the clinical significance of Gal-1 expression and its functional role in cell proliferation and invasion in epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN We evaluated the expression of Gal-1 in 52 serous, 11 endometrioid, and 3 mucinous type EOC tumour samples from 66 patients by immunohistochemistry. In vitro experiments were performed to determine the function of Gal-1 in cell survival, proliferation, and invasion in EOC cells using siRNA and anginex, a Gal-1 inhibitor, as well as recombinant Gal-1 protein. RESULTS Patients with strong Gal-1 peritumoural staining had poorer progression-free survival (PFS) than patients with weak peritumoural staining (p=0.03). Inhibition of Gal-1 by siRNA or anginex resulted in the inhibition of cell growth and proliferation of HeyA8 and SKOV3ip1 cells. Moreover, the ability of cells to migrate was significantly reduced by treatment of cells with Gal-1 siRNA but was increased by treatment of cells with recombinant Gal-1. When we evaluated the interaction between fibroblasts (T HESCs) and cancer cells (A2780-CP20), we found that MMP-2 expression in cancer cells was affected by Gal-1 secreted by fibroblast cells, which suggests that Gal-1 in human fibroblasts might affect the invasive abilities of tumour cells. CONCLUSION Our results suggest that Gal-1 expression is a potential prognostic factor for PFS and that Gal-1 could be a novel treatment target in EOC patients.

Prognostic value of pre-treatment circulating monocyte count in patients with cervical cancer: Comparison with SCC-Ag level

OBJECTIVE Higher level of circulating monocyte has been reported to be related with higher cancer incidence and mortality. We investigated the role of pre-treatment circulating monocyte count for cancer specific survival in cervical squamous cell carcinoma patients comparing with pre-treatment squamous cell carcinoma-related antigen (SCC-Ag) level. METHODS We retrospectively enrolled patients with squamous cell carcinoma of the cervix (FIGO stage IB to IVA) who had complete blood cell counts with differential cell count and serum SCC-Ag level within 2 weeks before starting initial treatment and were treated at Samsung Medical Center, Seoul, Korea, from 1996 to 2007. RESULTS The 788 patients in our study group had a median follow-up of 53.4 months and a five-year survival rate of 87.8%. The median value for pre-treatment circulating monocyte count was 349/μl (21-1463), and the median concentration of SCC-Ag was 1.6 ng/ml (0.1-362.0). In multivariable analysis, the pre-treatment circulating monocyte count was an independent prognostic factor for progression-free survival and overall survival in locally advanced disease (P=0.007 and P=0.038) but not in case of SCC-Ag for overall survival. The combined index of monocyte count and SCC-Ag level could enhance the prognostic value of SCC-Ag alone in patients with locally advanced cervical squamous cell carcinoma. CONCLUSIONS A higher pre-treatment circulating monocyte count is independently associated with poor prognosis in patients with locally advanced cervical squamous cell carcinoma. The pre-treatment circulating monocyte count may be considered as an adjunctive biomarker with SCC-Ag.

Accuracy of frozen section diagnosis of borderline ovarian tumors

OBJECTIVE To determine the correlation between the diagnosis of borderline ovarian tumors (BOTs) by frozen section and permanent histology analyses. METHODS Three hundred fifty-four pathology reports with diagnoses of BOTs by frozen section or permanent histology analysis at a single institution between 1995 and 2010 were evaluated with a review of the literature. Frozen section and permanent histology analyses were compared. Multivariate regression analysis was used to assess the influence of clinicopathological parameters on the likelihood of underdiagnosis. RESULTS The overall accuracy, i.e., agreement between frozen section and permanent histology diagnoses, was observed in 228 of 354 (64.4%) cases, yielding a sensitivity of 72.6%, a positive predictive value of 85.1%, underdiagnosis in 108 cases (30.5%), and overdiagnosis in 18 cases (5.1%). Based on multivariate analysis, mucinous histology (OR, 1.48; P=0.022) was the only significant predictor for underdiagnosis by frozen section. A comprehensive search of the literature identified 46 studies investigating the accuracy of frozen section analysis of BOTs. The data of 7 of 46 studies that met the criteria for inclusion and the data of the current study were pooled. The overall accuracy was 67.1% (741/1104), yielding a sensitivity of 82.1%, a positive predictive value of 78.7%, underdiagnosis in 222 cases (20.1%), and overdiagnosis in 141 cases (12.8%). CONCLUSIONS Frozen section analysis of BOTs has low accuracy, sensitivity, and positive predictive value, and underdiagnosis and overdiagnosis are frequent. Therefore, surgical decision-making for BOTs based on frozen section diagnosis should be done carefully, especially in tumors with mucinous histology.

Overexpression of annexin A4 is associated with chemoresistance in papillary serous adenocarcinoma of the ovary

Annexin A4 study in ovarian cancer has been primarily focused on clear cell carcinoma, which exhibits strong resistance to chemotherapy. The aim of this study was to examine the expression and cellular localization of annexin A4 in serous ovarian carcinomas. We evaluated the expression of annexin A4 with real-time polymerase chain reaction in 40 ovarian serous carcinoma tissues. Furthermore, the distribution of the protein within the tumor was studied by immunohistochemistry in 70 epithelial ovarian carcinoma tissues. The levels of annexin A4 transcripts were higher in 14 chemoresistant tumors than those in 26 chemosensitive tumors (P = .013). Immunohistochemical expressions showed that nuclear expression was detected in 14 (20.0%) of 70 samples, and cytoplasmic expression was detected in 17 (24.3%) of 70 samples. The results showed that 35.7% of women with nuclear expression were resistant to platinum-based chemotherapy, whereas only 14.3% of women without expression were chemoresistant (P = .065). In addition, patients with nuclear staining had significantly shorter disease-free survival than did patients who showed negative staining. Multivariate proportional hazards model revealed that the stage and nuclear annexin A4 expression were independent prognostic factors (hazard ratios, 6.34 [P = .001] and 2.85 [P = .011], respectively). This study showed that overexpression and nuclear localization of annexin A4 are related to chemoresistance and poor survival in patients with serous papillary ovarian carcinomas. Future studies are required to develop new therapies targeting annexin A4 in patients with ovarian epithelial adenocarcinoma.

Oncologic and reproductive outcomes in patients with advanced-stage borderline ovarian tumors

OBJECTIVE To evaluate the oncologic safety and reproductive outcomes in patients with advanced-stage borderline ovarian tumors (BOTs). STUDY DESIGN The medical records of patients with advanced-stage BOTs who were treated between 1997 and 2009 were reviewed retrospectively. Reproductive outcomes were assessed by telephone interviews. RESULTS Six (24%) and 19 patients (76%) had stages II and III disease, respectively. Twenty patients (80%) were treated by radical surgery and five patients (20%) underwent fertility-sparing surgery. Five patients (20%) had invasive implants and 20 patients (80%) had non-invasive implants. The median follow-up time was 71.4 months (range, 10-135 months). Four patients relapsed after a median interval of 40 months (range, 16-77 months) following primary treatment. Of these four patients, two who initially had invasive implants relapsed in the form of invasive ovarian carcinoma. Patients with invasive implants (2 of 5 [40%]) tend to relapse more frequently than patients with non-invasive implants (2 of 20 [10%]). Among five women who underwent fertility-sparing surgery, four attempted to conceive and five singleton pregnancies occurred. CONCLUSION Patients with advanced-stage BOTs with non-invasive implants have an excellent prognosis. Fertility-sparing surgery should be considered if there are no invasive implants. Indeed, reproductive outcomes after fertility-sparing surgery with non-invasive implants are promising.

Contributing factors for bone metastasis in uterine cervical cancer.

Objective The purpose of this study was to describe the clinical characteristics and to assess the contributing factors in patients developing bone metastasis in uterine cervical cancer. Methods Two thousand thirteen patients had a diagnosis of uterine cervical cancer at Samsung Medical Center between June 1994 and December 2011. During the study period, 105 patients with bone metastasis were identified, and their clinicopathologic data were investigated retrospectively. Results Among 105 patients with bone metastasis, 14 patients were excluded and 91 patients were evaluable. The median bone metastasis–free survival was 27 months (range, 0–279 months). The time to bone metastasis was significantly shorter in patients with adenocarcinoma than in patients with squamous cell carcinoma (median duration, 12 vs 29 months; P = 0.016). In addition, it was shorter in patients with stage IIB to stage IV disease than in those with stage I to stage IIA disease (15 vs 22 months; P = 0.02). The median survival after bone metastasis was 10 months, longer in the patients who received radiotherapy (± chemotherapy) than in the patients who received chemotherapy alone as a salvage therapy (12 vs 7 months; P = 0.01). Initial stage, number of bone metastases, location of involved bone, and coexisting metastatic lesion were not associated with the overall survival of the patients. Conclusions Our study demonstrates that adenocarcinoma, advanced stage (IIB-IV) and initial multiple bone metastases contribute to earlier bone metastasis. Once bone metastasis was recognized, the survival of these patients was poor and no factors were identified to predict survival of those patients.

Clinical significance of changes in peripheral lymphocyte count after surgery in early cervical cancer

OBJECTIVE Immune competence is an important prognostic factor in cancer patients. Surgical management of cancer can cause a variety of immunological disturbances, the clinical consequences of which are still unclear. MATERIALS AND METHODS Patients with clinically staged cervical carcinoma (IB to IIA) who were treated at Samsung Medical Center, Seoul, Korea from 1994 to 2007 were retrospectively enrolled. We compared peri-operative peripheral lymphocyte counts, tumor-infiltrating lymphocyte scores, and survival in patients with early cervical cancer treated by abdominal type III radical hysterectomy. RESULTS The sample included 756 patients. The median follow-up was 58 months with a range of 3-181 months. There was a positive correlation between pre-operative peripheral lymphocyte counts and tumor infiltrating lymphocyte score. Pre-operative peripheral lymphocyte counts decreased significantly after surgery. In multivariate analyses for recurrence, higher pre-operative peripheral lymphocyte counts and recovery of lymphocyte counts (more than 100/μL from the pre-operative level) on post-operative day 3 were independent positive prognostic factors and LN metastasis was negatively associated with post-operative recovery of peripheral lymphocyte counts. CONCLUSION Peripheral lymphocyte counts after cervical cancer surgery are important prognostic factors, and management aimed at minimizing immune disturbances after surgery should be assessed, especially in patients with LN metastasis.

Prognostic factors influencing decisions about surgical treatment of villoglandular adenocarcinoma of the uterine cervix.

Objective The objectives of this study were to analyze the clinicopathologic features of villoglandular adenocarcinoma (VGA) of the uterine cervix, a variant of cervical adenocarcinoma with good prognosis, and to discuss the association of human papillomavirus (HPV) infection with VGA. Methods A retrospective review of medical records was performed to identify the patients with VGA between 1999 and 2007 at the Samsung Medical Center. Results Fifteen patients were identified among 171 women diagnosed with adenocarcinoma of the cervix. The median age was 40 years (range, 32–72 years). Four patients were treated by cone biopsy and 10 patients by hysterectomy with or without pelvic lymphadenectomy. Five patients had invasion of more than half of the depth of tumor in the cervix. Lymphovascular space invasion was present in 2 patients, one of whom also had lymph node metastases. Three recurrences were identified during the median follow-up of 64 months (range, 9–149 months). An HPV test was positive in 6 of 7 patients. Of the 6 patients with HPV infection, 2 were positive for HPV type 18, one for HPV type 6, and the remaining 3 were positive for 1 or more types of high-risk HPV. Conclusions Although VGA has been reported to have a favorable prognosis, we observed recurrences in those patients with close margins by the tumor, lymph node metastasis, or advanced stage. Human papillomavirus DNA, mostly HPV types 16 and 18, was associated with VGA. Further studies are warranted on prognostic factors and the pathogenetic role of HPV infections.