Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

Expression of IL-18, IL-18 binding protein, and IL-18 receptor by normal and cancerous human ovarian tissues: possible implication of IL-18 in the pathogenesis of ovarian carcinoma.

Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P = 0.0007), IL-18BP levels were significantly higher in normal ovarian tissues (P = 0.04), and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P = 0.036). Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P = 0.025), while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

[Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?].

The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma.

The influence of early diagnosis of endometrioid endometrial cancer on disease stage and survival.

OBJECTIVE: To evaluate whether the presence or duration of uterine bleeding is associated with disease stage, and survival of patients with endometrioid endometrial carcinoma (EEC). METHODS: The records of 220 patients with EEC who underwent surgery were reviewed. The patients were divided into three groups according to the presence and duration of vaginal bleeding at the time of surgery. Group 1, without vaginal bleeding; group 2, vaginal bleeding up to 3 months; group 3, vaginal bleeding exceeding 3 months prior to surgery. Disease stage and survival were between the three groups. RESULTS: Of the 220 patients, 42 (19%) were asymptomatic; 95 (43%) had symptom duration of up to 3 months and 83 (38%) experienced bleeding for >3 months. There were no significant differences between groups 1, 2 and 3 regarding the proportion of patients with deep invasion in stage I (21, 24, 26%, p = 0.84; respectively), with grade 3 tumors (10, 13, 14%, p = 0.42; respectively) or with advanced stage disease (12, 14, 15%, p = 0.92; respectively). Survival analysis demonstrated a non-significant trend toward better survival in asymptomatic patients and in patients with a shorter duration of symptoms (p = 0.172). CONCLUSIONS: Diagnosis of EEC in asymptomatic patients or in patients with a short duration of bleeding is associated with comparable stage and survival.

Obstetric outcome following cervical conization.

OBJECTIVE: The purpose of the present study was to examine obstetric outcome of patients following conization and specifically the risk for preterm delivery (PTD). METHODS: A population-based study was performed comparing pregnancies in women following conization with those who had not undergone the procedure. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. RESULTS: Out of 104,670 deliveries, 53 women (0.05%) had undergone conization. Most conizations were performed using loop electrosurgical excision procedure (LEEP). Using multivariable analysis, the following conditions were significantly associated with conization: advanced maternal age, PTD before the 34th week, low birth weight, and cervical incompetence with cerclage. Higher rates of perinatal mortality were noted in pregnancies of women with conization, but after controlling for PTD, the association lost its significance. The risk of PTD <34 weeks was significantly higher than the comparison group (OR 7.73 95% CI 3.77-15.85, p < 0.001). This association remained significant after controlling for confounders, such as cervical incompetence, smoking, maternal age, birth order and year of delivery (OR 2.8 95% CI 1.3-6.1, p = 0.008). When comparing pregnancy outcomes of women with and without cerclage due to cervical incompetence, no significant differences were documented. CONCLUSIONS: A clear association exists between conization and PTD before the 34th week. This association persists after controlling for variables considered to coexist with PTD. Careful surveillance is required in pregnancies of women following conization for early detection of preterm contractions and PTD.

The rate of the predominant Jewish mutations in the BRCA1, BRCA2, MSH2 and MSH6 genes in unselected Jewish endometrial cancer patients.

OBJECTIVES: The genes associated with familial Endometrial Cancer (EC) are largely unknown. While EC is an integral part of Hereditary Non-Polyposis Colon Cancer, there is an ongoing debate if EC is indeed overrepresented in hereditary breast/ovarian cancer families. METHODS: Unselected Jewish women with EC who were diagnosed from January 1982 to January 2008 were genotyped for the predominant mutations in Jewish individuals in BRCA1 (185delAG, 5382InsC, Tyr978X) BRCA2 (6174delT), MSH2 (A636P, 324delCA) and MSH6 (c.3984_3987dup). RESULTS: Overall, 289 Jewish women with EC were included, the majority (217-75%) were Ashkenazim. Mean age at diagnosis was 62.6 ± 12 years, the most common histopathology was type I (endometrioid carcinoma) (80.4% of participants) with 29 having type II (Uterine papillary serous and clear cell cancer) Most patients (85.4%) had stage 1 disease by the FIGO staging. Five women (1.7%-2.3% of the Ashkenazim) carried either the BRCA1*185delAG (n = 4) or BRCA2*6174delT (n = 1) mutations, a rate similar with that of the general Ashkenazi population. Notably, none of 34 women with type II EC carried any BRCA1/BRCA2 mutations. Four (1.8%) and three (1.4%) of the 217 Ashkenazim patients harbored the c.3984_3987dup, A636P, MSH6 and MSH2 mutations, respectively, and 1/72 (1.4%) of the non-Ashkenazi patients harbored the 324delCA MSH2 mutation. Three of 42 (7.1%) women with EC diagnosed < 50 years carried either BRCA1 MSH6 or MSH2 mutations. CONCLUSIONS: Our data do not support screening for BRCA1/2 mutations in consecutive EC patients.

Three-dimensional power Doppler ultrasound in ovarian cancer and its correlation with histology.

PURPOSE: The aim of this study was to evaluate and quantify intraovarian blood flow with 3D power Doppler histogram analysis before surgical intervention in women suspected of having ovarian carcinoma and to determine the correlation with histology findings. METHODS: A prospective study was designed and 17 consecutive patients undergoing oophorectomy were included. Two groups of women were evaluated: high-risk women for ovarian pathologies and low-risk women with no known ovarian disease scheduled for bilateral oophorectomy for nonmalignant related pathology. Transvaginal ultrasound was performed using 2D, 3D-power Doppler ultrasound and histogram techniques. Four main parameters were evaluated: vascularization index (VI), flow index (FI), vascularization-flow index (VFI) and mean grayness (MG). Histological confirmation of the findings was done in all patients. Data were analyzed by the Mann-Whitney U test with P<0.05 considered as significant. RESULTS: Ultrasound scanning was performed for a total of 24 ovaries: 9 ovaries with cancer and 15 controls. There were no significant differences between the groups in all four histogram measurements: FI, VI, VFI and MG. There were no differences between the groups regarding ultrasound findings of free fluid in pelvis (16.7% in women with malignancy, 18.2% in women without ovarian malignancy; P=0.938) and the presence of complex ovarian cyst (83.8% in women with malignancy, 36.4% in women without ovarian malignancy; P=0.131). CONCLUSIONS: No significant differences were noted between benign and malignant ovaries in our population in all four indices of vascularity and perfusion of 3D power Doppler. Further large prospective studies should evaluate the significance of 3D power Doppler using histogram analysis in the early detection of ovarian cancer.

[Splenic metastases from female genital tract malignancies].

Splenic metastases are rare. Usually, they are part of a disseminated disease and located on the splenic capsule. Common sources are breast cancer, lung cancer and malignant melanoma. SoLitary splenic metastases are rare, usuaLLy located in the splenic parenchyma and metastasizing via the hematogenous route. Splenic metastases from ovarian carcinoma are usuaLly part of a disseminated disease, located on the splenic capsule and metastasize via the peritoneum. Splenic metastases from endometriaL carcinoma are usuaLLy solitary, Located in the splenic parenchyma and metastasize via the hematogenous route. Splenic metastases from cervical carcinoma are divided equally between metastases as part of a disseminated disease and soLitary metastases. Less than 100 cases of solitary splenic metastases have been reported with half of them being metastases from female genital tract malignancies: 30--ovarian carcinoma; 11--endometriaL carcinoma; 8--cervical carcinoma; and 1--tubal carcinoma. Few cases have been reported of splenic rupture because of metastases from choriocarcinoma. Splenic metastases as part of a disseminated disease are associated with poor prognosis, and splenectomy--apart from cases in which it might assist in achieving optimaL debulking--is not effective. Solitary splenic metastases represent a more moderate disease and the treatment of choice is splenectomy. SoLitary splenic metastases may be detected after an interval from the diagnosis of the primary disease. Hence, patients who had been treated for female genital tract malignancy, even if they are asymptomatic, need a long-term follow-up, including serial imaging studies of the spleen.

Splenic metastasis from endometrial carcinoma: report of a case and review of literature.

INTRODUCTION: Splenic metastasis from endometrial carcinoma is a rare clinical event, with only 11 cases documented previously in the literature. CASE REPORT: A 58-year-old woman had surgery and radiotherapy for stage IIB endometrial carcinoma. Eighteen months later, PET scan discovered a hypermetabolic splenic mass and two hypermetabolic lung nodules. Spleen biopsy showed metastasis from endometrial carcinoma. Chemotherapy with six cycles of cyclophosphamide, adriamycin and cisplatin effected a partial response of the splenic and lung metastasis. After few months, however, splenectomy was performed because of substantial growth of the spelnic metastasis and it confirmed that the splenic metastasis was of endometrial origin and solitary in the peritoneal cavity. After splenectomy, the patient received chemotherapy with six cycles of paclitaxel. To date, 6 months after splenectomy, she is alive with no intraperitoneal disease and with few stable lung metastases. CONCLUSION: This is the 12th reported case of splenic metastasis from endometrial carcinoma. Splenic metastasis from endometrial carcinoma is usually solitary splenic metastasis limited to the splenic parenchyma. Splenectomy is an appropriate treatment to avoid splenic rupture, splenic vein thrombosis and painful splenomegaly, to circumvent the splenic metastasis being a source of secondary metastatic disease, and to provide the potential for cure or extended survival. Since patients with splenic metastasis may be asymptomatic and the interval between the diagnoses of endometrial carcinoma and splenic metastasis may be prolonged, careful and extended follow-up after primary treatment of endometrial carcinoma is warranted.

Management of primary melanoma of the female urogenital tract.

Primary melanoma of the urogenital tract in women is rare, but biologically aggressive. They usually affect elderly women and account for less than 10% of all cancer of the urogenital tract in women and less than 10% of all melanoma diagnosed in women. Tumours originate from melanocytes that are present in the urogenital mucosal epithelium of about 3% of women. Tumour staging can be challenging; however, the American Joint Committee on Cancer melanoma staging system has been recommended for use in vulvar and vaginal melanoma. Surgery is the treatment of choice; less-extensive surgery can be a sensible approach because satisfactory locoregional control might be obtained from wide local excision and radiotherapy, without the morbidity and disfigurement associated with radical surgery. Complete regional lymphadenectomy does not seem necessary if a sentinel lymph-node biopsy sample is negative; however, this decision should be made with caution. Various chemotherapy and biotherapy (ie, immunotherapy and biological-response modifiers) regimens have been used in advanced or metastatic melanoma. However, the role of chemotherapy for women with urogenital-tract melanoma has not been established, and biotherapy methods presented to date have been anecdotal.

Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary.

BACKGROUND: We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. METHODS: The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. RESULTS: By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. CONCLUSION: The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further evaluated as potential diagnostic tools.

Uterine adenolipoleiomyoma: a tumor with potential of aggressive behavior.

An unusual uterine adenolipoleiomyoma forming intramural and subserosal masses and recurring within 16 months in the form of huge coalescent uterine masses is described. Histology showed the mass to be composed of benign-appearing smooth muscle, mature adipose tissue, and bland endocervical-type glands. The recurrent adenolipoleiomyoma contained, in addition, benign-appearing endometrial-type glands and stroma and showed small foci of atypically proliferating endocervical-type epithelium. This is the fourth report of adenolipoleiomyoma within the uterus, the second with an intramural location, and the first with an aggressive behavior in the form of massive local recurrence.

MMP-2, TIMP-1, E-cadherin, and beta-catenin expression in endometrial serous carcinoma compared with low-grade endometrial endometrioid carcinoma and proliferative endometrium.

OBJECTIVE: To investigate the expression of MMP-2, TIMP-1, E-cadherin and beta-catenin in endometrial serous carcinoma (ESC), low-grade endometrial endometrioid carcinoma (EEC), and proliferative endometrium. METHODS: We performed an immunohistochemical study on 14 cases of ESC, 15 cases of low-grade EEC, and 10 cases of proliferative endometrium. RESULTS: Compared with low-grade EEC, ESC showed significantly increased MMP-2 and TIMP-1 expression, as well as decreased membranous beta-catenin staining. E-cadherin expression was significantly lower in ESC and EEC as compared with proliferative endometrium. CONCLUSIONS: We suggest that MMP-2 and TIMP-1 expression and loss of beta-catenin have a role in the pathogenesis and progression of ESC. Decreased E-cadherin may have an important role in the development of both ESC and EEC. Furthermore, the dissimilarities in MMP-2, TIMP-1, E-cadherin and beta-catenin expressions in ESC compared with EEC may be responsible, along with other factors, for their different biological behavior.

Matrix metalloproteinases 2 and 9, E-cadherin, and beta-catenin expression in endometriosis, low-grade endometrial carcinoma and non-neoplastic eutopic endometrium.

OBJECTIVES: Endometriosis and endometrial endometrioid carcinoma are both capable of invasion and metastasis, but their biological behavior is strikingly different. Matrix metalloproteinases (MMPs) and changes in adhesion molecules have a role in the pathogenesis of various physiological and pathological processes, as well as in the development of endometriosis and endometrioid endometrial carcinoma. We hypothesized that endometriosis, being a benign process, will show different MMPs and adhesion molecules expressions, compared to endometrioid endometrial carcinoma, a disease with potential of malignant behavior. STUDY DESIGN: We performed an immunohistochemical study to investigate expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin and beta-catenin in endometriosis, low-grade endometrial endometrioid carcinoma, and eutopic proliferative endometrium. Endometriotic tissues (n=15), low-grade endometrial endometrioid carcinomas (n=15), and unremarkable proliferative endometrium from women without endometriosis or carcinoma (n=10) were examined. RESULTS: Endometriotic tissues showed statistically significantly stronger staining for MMP-9 and reduced beta-catenin expression when compared with proliferative endometrium. Endometrial endometrioid carcinoma showed decreased E-cadherin expression in comparison with proliferative endometrium. MMP-2 and MMP-9, and E-cadherin expressions were significantly higher and beta-catenin expression was significantly lower in endometriosis as compared to endometrioid carcinoma. CONCLUSIONS: We suggest that increased MMPs and altered beta-catenin may play a role in the pathogenesis of endometriosis. Decreased E-cadherin may be important in the development of endometrial endometrioid carcinoma. The changes in MMPs, E-cadherin and beta-catenin differ in endometriosis from those in endometrioid carcinoma, an interesting finding in view of the fact that both these diseases are capable of invasion and metastasis, but have different biological behavior.

Ovarian signet-ring stromal tumor: a potential diagnostic pitfall.

Signet-ring stromal tumor is a rare ovarian neoplasm with only 10 reported cases in the literature. We report an unusual case of ovarian signet-ring stromal tumor in a 69-year-old woman who presented with right adnexal mass and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis was based on histological, histochemical, immunohistochemical, and electron microscopy characteristics. The main significance is to differentiate this benign tumor from the highly malignant Krukenberg tumor, and this differential diagnosis is discussed.

[Hypercalcemia in malignancies of the female genital tract].

Hypercalcemia is the most common paraneoplastic syndrome in adult malignancies (10%-30%) and rare in pediatric cancers (0.5%-1.3%). Hypercalcemia in malignancies is categorized into two groups: 1) Humoral hypercalcemia of malignancy (HHM)-caused by substances that are produced by the tumor cells and secreted into the blood circulation such as parathyroid hormone-related protein (PTH-rP), parathyroid hormone-intact (PTH-i), the enzyme 1-alpha-hydroxylase that catalyzes the synthesis of the active form of vitamin D (1,25-dihydroxyvitamin D3), and other substances; 2) Hypercalcemia due to bone destruction by metastases. Hypercalcemia occurs in less than 5% of female genital tract malignancies and virtually in all cases (95%) it is HHM. Female genital tract malignancy-associated HHM is caused most often (80%) by PTH-rP. Ovarian cancer is the most common female genital tract malignancy that is associated with HHM. Although HHM occurs in only 5% of ovarian cancers, it occurs in a relatively high percentage in the following rare ovarian tumors: a). Small cell carcinoma of the ovary - a rare tumor that accounts for only 1% of all ovarian cancers and is associated with HHM in 66% of the cases; b). Clear cell carcinoma of the ovary - an uncommon tumor that accounts for 5% of all ovarian cancers and is associated with HHM in 5%-10% of the cases. Since dysgerminoma is the most common malignant ovarian tumor in children, in girls it is the second most common ovarian neoplasm, after ovarian small cell carcinoma, to be associated with HHM.

Chemiluminescent optical fiber immunosensor for detection of autoantibodies to ovarian and breast cancer-associated antigens.

We report herein the development of an optical fiber based chemiluminescent immunosensor for detection of the native autoimmune response to GIPC-1, a PDZ containing protein involved in regulation of G-protein signaling. The recombinant protein GIPC-1 was expressed in bacteria, purified, refolded and conjugated to the tip of an optical fiber. A human monoclonal 27.B1 IgM isolated from a breast cancer patient, which targets the GIPC-1 protein, was used for calibration of the immunosensor and was detected down to a concentration of 30 pg/ml. We determined that the fiber-optic immunosensor had a detection limit 50 times lower than chemiluminescent ELISA, and approximately 500 times lower than colorimetric ELISA. In addition, sera from 11 ovarian cancer patients, 22 breast cancer patients and asymptomatic controls were tested for the presence of IgM anti-GIPC-1 autoantibodies in their serum using the two methods. The immunosensor assay detected 54% and 77% GIPC-1 positive sera within ovarian and breast cancer patients, respectively, as compared to chemiluminescent ELISA, which only detected 18% and 27%, respectively. We envision that this immunosensor may serve as a diagnostic tool for screening women for ovarian and breast cancer at an early stage, thus increasing their chance of survival.

Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6.

BACKGROUND: Cancerous ovarian tissues contain and produce high levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-alpha). The aim of this study was to assess the mechanisms by which autocrine IL-6 affects the ovarian carcinoma continuous cell line (SKOV-3) tumorigenicity. MATERIALS AND METHODS: Autocrine IL-6 was neutralized by the addition of anti-IL-6 antibodies to SKOV-3 cell cultures. The proliferation rate was evaluated by MMT staining and the capacity to produce matrix metalloproteinases (MMPs) 2 and 9 was examined by zymography. RESULTS: The SKOV-3 cells secreted IL-6 in a time-dependent manner (24-96 h). The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their proliferation rate within 96 h of incubation. In addition, SKOV-3 cells secreted MMP-2 and MMP-9 as confirmed by zymography. The MMP-9 levels decreased in a time-dependent manner (3, 8, 24 h) and the addition of anti-IL-6 antibodies to SKOV-3 cell cultures significantly decreased their capacity to secrete MMP-9, particularly after 8 h of incubation. MMP-2 (pro-active and active forms) was also secreted by SKOV-3 cell cultures but could be measured only after 24-96 h of incubation. The levels of MMP-2 increased in a time-dependent manner. The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their capacity to secrete MMP-2. CONCLUSION: Our results suggest that IL-6 secreted by SKOV-3 cells could be involved in their tumorigenic potential, particularly potentiating their capacity to secrete MMP-9.

Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

OBJECTIVE: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. METHODS: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. RESULTS: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. CONCLUSIONS: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.