CA 125 as an independent prognostic factor for survival in patients with epithelial ovarian cancer

Serum CA 125 levels (upper normal value less than 35 U/ml) determined before surgery and 3 months after surgery were evaluated as independent prognostic factors for survival in patients with epithelial ovarian carcinomas. In 163 women preoperative serum levels of CA 125 (p = 0.13) gave no additional information with regard to the relationship of survival prognosis to histologic grade (p = 0.04) and to the diameter of residual tumor mass (p = 0.03). In 132 patients serum CA 125 levels were also determined 3 months after surgery and reflected the effectiveness of the first two cycles of postoperative cytotoxic treatment. At that time CA 125 was the strongest independent prognostic factor for survival (p = 0.0006 Cox model), as compared with histologic grade (p = 0.06), International Federation of Gynecology and Obstetrics stage (p = 0.15), and diameter of residual tumor mass (p = 0.66). Therefore, we concluded that serum CA 125 levels determined 3 months after surgery can identify a high-risk population among patients with epithelial ovarian carcinomas for whom a more aggressive or more intensive treatment might be beneficial.     

CA 125 measured before second-look laparotomy is an independent prognostic factor for survival in patients with epithelial ovarian cancer

The prognostic significance of serum CA 125 level measured in the week before second-look operation was evaluated in 208 patients with invasive epithelial ovarian cancer. Serum CA 125 level was greater than 35 U/ml in 44.7% of patients. All patients with pathological complete response (PCR) had a serum CA 125 level less than or equal to 35 U/ml except one who developed lung metastases 2 months later. The sensitivity of serum CA 125 for identifying residual tumor at second-look operations was 58%, the specificity was 98%, the predictive value of a positive test was 99%, and the predictive value of a negative test was 43%. By Cox regression analysis, tumor state of second look, serum CA 125 level, histologic type, FIGO stage, and tumor grade were identified as independent prognostic factors for survival. We conclude that measurement of serum CA 125 level after induction chemotherapy represents a noninvasive method to identify patients at high risk for subsequent death from ovarian cancer. As far as we know, this is the first report to identify serum CA 125 level as an independent prognostic factor at the time of second-look laparotomy.     

Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer

OBJECTIVE: Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM overexpression in EOC. METHODS: We assessed by immunohistochemistry the expression of the Ep-CAM antigen on tissue microarrays containing paraffin-embedded tissue samples of 199 patients with documented EOC. Patients were operated for ovarian cancer in the period between June 1980 and January 2000. RESULTS: We observed a rate of Ep-CAM overexpression of 68.8%. Ep-CAM overexpression was significantly related to a decreased overall survival (P = 0.036). The prognostic power of Ep-CAM overexpression was particularly strong in patients with stage III and IV disease. In fact, in this subgroup, median overall survival was twofold higher in patients without as compared to patients with Ep-CAM overexpression (46 vs. 23 months, P < 0.01). Univariate analysis revealed a correlation with histologic grade. We observed a significantly higher rate of Ep-CAM overexpression (83.5%) in grade 3 tumors. Histologic subtypes associated with a higher rate of Ep-CAM overexpression were serous carcinoma, squamous cell carcinoma, undifferentiated carcinoma, clear cell carcinoma, and endometrioid carcinoma. Cox regression analysis showed Ep-CAM overexpression to be an independent prognostic marker (P = 0.037, RR = 1.64). CONCLUSIONS: This retrospective analysis demonstrates for the first time an independent prognostic value of Ep-CAM overexpression in patients with EOC. Ovarian cancer patients with Ep-CAM overexpressing tumors are frequent and would qualify for treatment with Ep-CAM-specific immunotherapeutic approaches.     

The preoperative albumin level is an independent prognostic factor for optimally debulked epithelial ovarian cancer

Purpose

A low albumin level has been reported to be a prognostic factor for various cancers. The aim of this study was to determine the association between preoperative serum albumin level and survival in patients with epithelial ovarian cancer (EOC).

Methods

Records of 337 patients with EOC that underwent optimal cytoreductive surgery were retrospectively reviewed. Threshold albumin level was planned as 32.5 g L^?1 due to the statistical analyses.

Results

Mean overall survival was 51.5 months. Area under the ROC curve was found statistically significant for the discriminative role of albumin for survival outcome (AUC = 0.857, 95% CI 0.813–0.90, P < 0.001). The best cut-off point for albumin was determined as 32.5 g L^?1. The sensitivity rate, specificity rate, positive and negative predictive values, and accuracy rate for this cut-off level were found 67.2, 91.2, 81.2, 83.1, and 82.5%, respectively. Preoperative hypoalbuminemia was noted in 101 (30.0%) of the patients, of which 6.2% had an albumin level <25 g L^?1. The albumin level was independently and significantly associated with overall survival (HR 2.6; 95% CI 2.1–3.1; P < 0.001). Subgroup analysis showed that patients with an albumin level <32.5 and ≥32.5 g L^?1 had mean estimated overall survival of 40.6 and 96.0 months, respectively. Age, stage, and presence of ascites were the other independent significant factors.

Conclusions

The preoperative albumin level is an independent prognostic factor for overall survival in optimally debulked EOC patients. Further investigations about preoperative albumin level in prognostic models will contribute to the literature.

     

Age as a prognostic factor in epithelial ovarian carcinoma

Summary. One prognostic factor in epithelial ovarian cancer appears to be the patient's age at presentation. We have retrospectively analysed data from 2305 patients with this tumour in East Anglia during the period 1960–1980. The influence of age as a factor in survival was studied by comparing outcome in young patients between the ages of 15 and 35 (3.1% of all cases) with the outcome in the women over 35. The prognosis was significantly better in young patients, even when age correction is applied. This has implications for the management of patients with this common tumour.     

Age as a prognostic factor in epithelial ovarian carcinoma

One prognostic factor in epithelial ovarian cancer appears to be the patient's age at presentation. We have retrospectively analysed data from 2305 patients with this tumour in East Anglia during the period 1960-1980. The influence of age as a factor in survival was studied by comparing outcome in young patients between the ages of 15 and 35 (3.1% of all cases) with the outcome in the women over 35. The prognosis was significantly better in young patients, even when age correction is applied. This has implications for the management of patients with this common tumour.     

Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer

OBJECTIVE:To estimate the association of preoperative CA 125 levels with outcome in primary ovarian cancer patients.METHODS:One hundred forty-two patients with epithelial ovarian cancer, who had a serum CA 125 level drawn before surgery, were retrospectively evaluated. The relationship of preoperative CA 125 levels and various preoperative and postoperative variables was evaluated. CA 125 levels were determined using a solid-phase immunoassay.RESULTS:The median CA 125 value for all patients was 582 U/mL (range 7-52,930 U/mL). Preoperative CA 125 values did not correlate with increasing age (P =.40), but were found to be significantly associated with serous histology compared with other histology (median CA 125 of 870 versus 334 U/mL, P =.02), high-stage (III/IV) compared with low-stage (median CA 125 of 893 versus 174 U/mL, P <.001), high tumor grade (3) compared with grade 1 or 2 (median CA 125 of 928 versus 323 U/mL, P <.001), and the presence of ascites compared with absence of ascites (median CA 125 of 893 versus 220 U/mL, P <.001). Suboptimal cytoreduction (more than 1 cm residual) was associated with significantly higher CA 125 levels (1067 U/mL) compared with individuals with optimal cytoreduction (399 U/mL, P <.001). Preoperative CA 125 values less than 500 U/mL had a positive predictive value for optimal cytoreduction of 82%, but a poor negative predictive value of 48%. After adjusting for covariates, there was a significant association between CA 125 levels and disease-specific survival. As preoperative CA 125 levels increased, the risk of death increased except at the highest values of CA 125.CONCLUSION:Preoperative CA 125 is an independent risk factor for death due to disease in ovarian cancer, but not a reliable predictor of optimal cytoreduction.     

Wee1 is a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions

Objective

Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III–IV) ovarian serous carcinoma.

Methods

Wee1 protein expression was analyzed in 287 effusions using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. Forty-five effusions were additionally studied using Western blotting. Wee1 was further silenced in SKOV3 and OVCAR8 cells by siRNA knockdown and proliferation was assessed.

Results

Nuclear expression of Wee1 in tumor cells was observed in 265/287 (92%) and 45/45 (100%) effusions by immunohistochemistry and Western blotting, respectively. Wee1 expression by immunohistochemistry was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis (p = 0.002). Wee1 silencing in SKOV3 and OVCAR8 cells reduced proliferation. In univariate survival analysis of the entire cohort, a trend was observed between high (> 25% of cells) Wee1 expression and poor overall survival (p = 0.083). Survival analysis for 109 patients with post-chemotherapy effusions showed significant association between Wee1 expression and poor overall survival (p = 0.004), a finding which retained its independent prognostic role in Cox multivariate analysis (p = 0.003).

Conclusions

Wee1 is frequently expressed in ovarian serous carcinoma effusions, and its expression is significantly higher following exposure to chemotherapy. The present study is the first to report that Wee1 is an independent prognostic marker in serous ovarian carcinoma.     

CA125 regression during neoadjuvant chemotherapy as an independent prognostic factor for survival in patients with advanced ovarian serous adenocarcinoma

OBJECTIVE: The associations of the CA125 regression rate with initial response to chemotherapy and prognosis remain unclear. We examined the association between CA125 regression in neoadjuvant chemotherapy (NAC) and prognosis. METHODS: Fifty patients with advanced ovarian cancer (TNM classification TIIIc or M1) who received initial NAC and did not undergo significant cytoreductive surgery were selected for the retrospective analysis, after excluding clear cell carcinoma and mucinous adenocarcinoma putative to be cisplatin-resistant. For each patient, regression coefficient was calculated using all the CA125 levels measured from the day of NAC as day 0 until the day of normalization of CA125 level (<35 IU/ml) or the day of standard surgery. Responder was defined as a regression coefficient of -0.039 or greater (33 cases) and nonresponder as a regression coefficient less than -0.039 (17 cases). RESULTS: The 3-year survival rate for all 50 cases was 59.3%. When stratified by regression coefficient of CA125 levels, the 3-year survival was 70.5% in responders and 43.3% in nonresponders. Univariate analysis identified the regression coefficient of CA125 as a significant prognostic factor for overall survival (P = 0.012; log lank test). Residual tumor at standard surgery after NAC and absolute CA125 level were not significant prognostic factors. CONCLUSIONS: Based on the CA125 regression rate, it is possible to stratify TIIIc or M1 ovarian serous adenocarcinoma cases into those with a good prognosis of survival and those with poor prognosis. Regression coefficient of CA125 level greater than -0.039 predicts good 3-year survival after subsequent radical surgeries.     

Serum C-reactive protein as a prognostic factor in patients with epithelial ovarian cancer

OBJECTIVE: It is well known that the serum level of Interleukin-6 (IL-6) correlates with the level of C-reactive protein (CRP). The purpose of this study is to determine the significance of CRP as a prognostic factor in epithelial ovarian cancer. STUDY DESIGN: The present study is comprised of 120 patients with epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50 mg/l were considered high CRP. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with poor survival. RESULTS: The serum CRP value was significantly associated with the volume of ascites (P = 0.000004). Univariate analysis showed that the FIGO stage, primary tumour diameter, size of residual tumour, histologic grade, volume of ascites and high serum level of CRP were significant prognostic factors. Cox's multivariate proportional hazard model showed that histologic grade was the most important prognostic factor (P = 0.0026). FIGO stage and volume of ascites were also independent factors for 5-year survival (P = 0.0310 and P = 0.0216, respectively). However, the serum CRP value was not an independent prognostic factor. CONCLUSION: CRP is an adverse prognostic factor in univariate analysis, but not in multivariate analysis.     

Nuclear shape: An independent predictor of survival in patients with ovarian carcinoma

Geisler JP, Geisler HE, Wiemann MC, Givens SS, Zhou Z, Miller GA. Nuclear shape: An independent predictor of survival in patients with ovarian carcinoma. Int J Gynecol Cancer 1998; 8 : 164–167.
Since nuclear morphometry has recently been shown to be of prognostic value in several malignancies, including endometrial cancer, the authors attempted to see if those same morphometric features of nuclear size, shape and summed optical density had an impact on survival in patients with epithelial malignancies of the ovary. Eighty-three consecutive patients with epithelial malignancies of the ovary had their tumors studied in a quantitative manner evaluating nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD). Touch preps from this tissue were made. Patient records were examined for FIGO stage, grade, histology, as well as level of cytoreduction. The mean follow-up was 37 months (median 30 months, range 24–55 months). Multivariate analysis proved that the level of cytoreduction ( P = 0.0002), FIGO stage ( P = 0.025), and NUSH ( P = 0.036) were independent predictors of survival. NUSH ( P = 0.018) and NUSD ( P = 0.020) were significantly different among the different histologic grades. Additionally, NUSH ( P = 0.007) and NUSD ( P = 0.001) were significantly different between patients who did and did not survive. NUSZ was not significantly related to survival, stage, grade or level of cytoreduction. In conclusion, NUSH and NUSD both appear to be important morphometric features in epithelial ovarian carcinoma. Further study concerning their applicability as prognostic factors is warranted.     

Value of glutathion-S transferase pi as a prognostic factor in epithelial ovarian carcinoma

The association between glutathione S-transferase pi (GSTpi) and other clinicopathological parameters, response to chemotherapy and clinical outcome were investigated in chemotherapy naive epithelial ovarian cancer patients. Paraffin-embedded material from 55 patients were used for immunohistochemical analysis. All patients had received six cycles of cisplatinum-based chemotherapy and 41 of them were revalued by laparotomy. Pre- and post-chemotherapy GSTpi staining were detected in the cancer tissues of 18/55 (32.7%) and 5/14 (35.7%) patients, respectively. GSTpi expression was not associated with other clinicopathologic parameters. Of 17 patients with postoperative measurable residual disease clinical response was observed in 4/7 of GSTpi positive and in 9/10 GSTpi negative patients (p = 0.25). Pathologic complete response (pCR) was achieved in 5/8 of GSTpi positive and 11/22 of GSTpi negative cases (p = 0.69). There was no significant difference in overall survival and progression-free survival (PFS) according to initial GSTpi status. However the PFS of the five patients (median 22 +/- 5.9 months) who had postchemotherapy positive GSTpi was significantly shorter than the nine patients (10.0 +/- 2.19 months) who had negative GSTpi (p = 0.006). This difference was not observed in overall survival. These results suggest that initial immunohistochemical staining of GSTpi does not aid in the prediction of pCR and clinical outcome in patients with epithelial ovarian cancer. Nonetheless investigation of GSTpi expression after chemotherapy needs further evaluation.     

Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases

OBJECTIVES: The aim of this study was to determine the value of optimal cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective review was performed of 37 women with stage IV epithelial ovarian cancer treated by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV because of the presence of liver metastases alone. Although no patients died within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50 days after primary surgery. The overall median survival was 11 months with overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate analysis comparing age, histological type, tumor grade, place of surgery, secondary surgical procedure, performance of bowel surgery, presence of liver metastases, and optimal cytoreduction, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained highly significant (P = 0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were designated as having stage IV disease because of the presence of liver metastases, by multivariate analysis, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023 and 0.036, respectively). Site of metastases designating stage IV status was not associated with a reduced likelihood of achieving optimal debulking (P = 0.18). CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian cancer with or without hepatic metastases is associated with a more favorable outcome survival.     

Lymph node sampling is of prognostic value in early stage epithelial ovarian carcinoma

PURPOSE: The importance of lymph node involvement as a prognostic factor is still under debate. In the present study, the impact of surgical staging for prognosis in early stages of epithelial ovarian cancer was evaluated in a series of 113 patients. MATERIAL AND METHODS: A retrospective study was carried out at the Department of Gynecological Oncology, Orebro University Hospital, during the period 1994-1998. In a subgroup of 20 out of 113 patients, pelvic lymph node sampling or pelvic lymphadenectomy was included in the standard surgical procedure. In cases of positive lymph nodes, the tumors were upstaged to FIGO Stage III. Pearson's chi-square, the t-test, the log-rank test and Cox multivariate analysis were used in the statistical analyses. RESULTS: The 20 patients with lymph node sampling or lymphadenectomy were compared with the remaining 93 patients without a comprehensive surgical staging procedure. A survival analysis demonstrated a significant (p = 0.005) difference in disease-free survival rates between the two subgroups, where there was a survival benefit in the subgroup of patients who had undergone comprehensive surgical staging. In a Cox proportional hazard regression analysis with disease-free survival as the endpoint, high tumor grade (HR = 3.14) and comprehensive surgical staging with at least a node sampling (HR = 0.09) were significant and independent prognostic factors. CONCLUSION: The benefit in survival after the procedure of lymph node sampling in early stages of epithelial ovarian carcinoma could probably be explained by the fact that the surgical procedure detects otherwise unrecognized Stage III disease.     

The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer

Background

The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.

Methods

The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(?) cells).

Results

The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P?=?0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(?) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(?) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(?) cells than in RECQL1(+) cells.

Conclusions

These results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.

     

血清CA125值的变化对判断上皮性卵巢癌疗效及预后的临床研究

目的 探讨化疗前后CA125变化对上皮性卵巢癌疗效、预后判定的临床价值.方法 对北京协和医院1989-12-01-2001-12-01初治的203例上皮性卵巢癌患者进行血清CA125的检测,计算化疗2疗程后血清CA125值较化疗前下降的百分比,观察CA125不同组复发中位时间及生存期限的差异.结果 203例患者中有102例复发,CA125下降≥75%组、50%～<75%组、<50%组各组复发的中位时间差异有显著性(F=8.422,P<0.001),且CA125下降<50%组的复发时间短;Kaplan-Meier法计算生存率,得出化疗2疗程后CA125值下降水平≥75%组的中位生存时间为42.8个月,50%~<75%组为34.6个月,<50%组为24.0个月,CA125上升组为9.3个月,以log-rank时序检验比较各组生存率曲线的分布差异有显著性(X2=33.097,P<0.001);COX风险模型分析上皮性卵巢癌预后的多因素结果表明CA125下降水平、FIGO分期、术后残存病灶大小与卵巢上皮癌预后明显相关.结论 化疗2疗程后CA125值与化疗前下降的百分比对上皮性卵巢癌的预后评定有一定的临床价值,检测该指标可协助判断复发,尽早予以相应的治疗措施.