Cigarette smoking and epithelial ovarian cancer by histologic type

OBJECTIVE: To examine cigarette smoking as a risk factor for different types of epithelial ovarian cancer. METHODS: We used data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case control investigation. Cases were 447 women aged 20-54 years with diagnoses of epithelial ovarian cancer. Controls were 3868 women selected by random-digit dialing. Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) as estimators of the relative risk of ovarian cancer. With age and study site as conditioning variables, OR point estimates were additionally adjusted for parity and use of oral contraceptives. RESULTS: The OR of mucinous epithelial ovarian cancer for women who had ever smoked was 2.3 (95% CI 1.4, 3.9) and for current smokers was 2.9 (95% CI 1.7, 4.9). The OR of mucinous tumors for current smokers was significantly elevated regardless of years since first cigarette or age at which women first smoked. The OR of mucinous tumors for current smokers increased slightly as cumulative pack-years of smoking increased, although the trend was not significant. Similar patterns of elevated risk were not observed among serous, endometrioid, or other histologic types. Odds ratio point estimates for former smokers were not significantly elevated for any histologic type. CONCLUSION: Current cigarette smoking was a risk factor for mucinous epithelial ovarian cancer, but not other histologic types.     

Prognostic value of histologic grading of ovarian carcinomas.

Histologic grading of ovarian carcinomas has prognostic and therapeutic relevance, but although several grading systems have been proposed, no universal grading system has been established. Silverberg's group has recently proposed a simple histologic grading system of ovarian carcinomas. We studied its prognostic value in 70 patients with invasive ovarian carcinomas and compared it with that of histologic typing and clinical staging. Kaplan-Meier survival curves showed the following 5-year survival rate using the Silverberg grading system: grade I (n=21) 91%, grade II (n=20) 64%, grade III (n=29) 38% (p<0.001). Multivariate analysis indicated that the histologic grade, the clinical stage, and clear cell histologic type were significant prognostic factors. The Silverberg histologic grade correlated well with prognosis for all histologic types of ovarian carcinomas except for clear cell carcinoma. It is simple, reproducible, and provides useful prognostic information.     

Comparison of early-stage primary serous fallopian tube carcinomas and equivalent stage serous epithelial ovarian carcinomas

ObjectiveTo investigate the outcome of patients with early-stage primary fallopian tube carcinomas (PFTC) and those of patients with equivalent-stage serous epithelial ovarian carcinomas (SEOC).Materials and methodsA balanced and matched, case–control comparison was conducted in a university-based tertiary hospital database between 1978 and 2007. All PFTC and SEOC patients were treated with complete staging surgery followed by multiagent chemotherapy. One SEOC control was matched for each PFTC patient in a very uniform manner (characteristics and treatment). Disease-free survival (DFS) and overall survival (OS) were then compared using Kaplan-Meier analysis.ResultsTwenty-six paired patients were analyzed. Patients with PFTC were significantly older than the SEOC patients (58 years vs. 51 years, p = 0.001). In terms of recurrence, PFTC patients frequently had an extra-abdominal metastasis (3/4, 75%), in contrast to the SEOC patients, who did not (1/5, 20%). The 5-year DFS rate was similar in both groups (85% vs. 81%, p = 0.05), contributing to a similar OS rate (89% vs. 85%, p = 0.50). The median DFS and OS of patients with PFTC and SEOC were also similar without a statistically significant difference (125 months vs. 109 months, and 125 months vs. 122 months, respectively).ConclusionOur study demonstrated that the survival outcome of International Federation of Gynecology and Obstetrics (FIGO) I/II PFTC patients was similar to that of FIGO I/II SEOC patients, and both groups had a >80% 5-year DFS rate after complete staging surgery, followed by multiagent chemotherapy. This finding is worthy of being investigated.     

Histological grading of epithelial ovarian carcinomas.

The grade of an ovarian epithelial neoplasm provides useful information. However, different approaches to grading exist and many ovarian cancers are not graded. We examined primary ovarian cancers from patients treated at our hospital and applied the 'universal' grading system. We found a significant association between grade and clinical stage, with a survival difference between grades for low-stage tumours. The application of grade is discussed in the light of developments in the grading of other gynaecological cancers.     

Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data.

Surface epithelial tumors are a large and heterogeneous group of neoplasms that are subclassified based on cell type and malignant potential. The objective of this review is to examine the correlations between recent molecular pathology data and the traditional histopathologic classification of surface epithelial tumors. By doing so, 6 distinct subsets of ovarian epithelial neoplasia can be identified with potential treatment implications 1. high-grade serous, high-grade endometrioid, and undifferentiated carcinomas; 2. low-grade serous carcinomas and serous borderline tumors; 3. mucinous carcinomas and mucinous borderline tumors of intestinal type; 4. low-grade endometrioid carcinomas and endometrioid borderline tumors; 5. clear cell carcinomas; and 6. transitional cell carcinomas.     

Reproducibility and prognostic value of histologic type and grade in early epithelial ovarian cancer

From September 1981 to September 1986, 417 consecutive treated patients with epithelial ovarian cancer FIGO stage I and II were registered by the Danish Ovarian Cancer Group (DACOVA). Typing and grading were primarily performed by several pathologists, with and without training in gynecologic pathology. Review typing by one specially trained pathologist showed an agreement rate of 72% for serous and endometrioid carcinoma, 86% for mucinous and 100% for clear cell carcinoma. The agreement rate was calculated for patients primarily classified by pathologists trained in gynecologic pathology and for patients primarily classified by pathologists with and without training. The agreement rate was not better for the group of pathologists with special training in gynecologic pathology. Grading was performed according to two classifications: one based on architectural pattern and one on combined criteria. Review grading showed an agreement rate of 77% for architectural classification and an agreement rate of 52% for combined classification. The agreement rate between the two grade classifications at review was only 62%. Combined grading showed a significant tendency towards classifying more tumors as low grade. All grade classifications had prognostic value. The poor agreement rate of both type and grade even when performed by pathologists with expertise in gynecologic pathology, calls for a better and more reproducible characterization of malignant ovarian tumors.     

Pattern of lymph node metastases in clinically unilateral stage I invasive epithelial ovarian carcinomas

PURPOSE: There is controversy regarding the pattern of lymphatic spread in unilateral stage I invasive ovarian carcinomas. The purpose of this study is to describe the incidence and distribution of lymph node (LN) metastases in ovarian carcinomas clinically confined to one ovary. METHODS: Ninety-six patients with disease visibly confined to one ovary were identified. Pathology reports were reviewed to identify metastatic LN involvement, number of involved nodes, and their locations. Patients with gross disease in the pelvis or abdomen or those who had grossly positive LNs removed for debulking were excluded from this review. RESULTS: Fourteen of ninety-six patients (15%) had microscopically positive LNs on pathologic review. All of these 14 patients had grade 3 tumors. Grade 3 tumors were more commonly seen in LN-positive versus LN-negative patients (P < 0.001). Pelvic nodes were positive in 7 patients (50%), paraaortic nodes in 5 patients (36%), and both in 2 patients (14%). Forty-two patients had LN sampling only on the side ipsilateral to the neoplastic ovary, 4 of whom (10%) had LN metastases. Fifty-four patients had bilateral sampling performed, 10 of whom (19%) had LN metastases. Of these 10 patients, isolated ipsilateral LN metastases were seen in 5 (50%) cases. Isolated contralateral LN metastases were seen in 3 (30%) cases, and bilateral metastases were seen in 2 (20%). CONCLUSIONS: In this cohort of patients with clinical stage I ovarian carcinoma with disease limited to one ovary, bilateral LN sampling increased the identification of nodal metastases. Ipsilateral sampling may result in the understaging of patients. Bilateral pelvic and paraaortic LN sampling is recommended to accurately stage ovarian carcinoma.     

早期卵巢上皮性癌保留生育功能治疗

随着肿瘤发病年龄的年轻化，如何保留肿瘤患者生育功能已成为肿瘤治疗中的热点问题。卵巢癌是最常见的妇科恶性肿瘤之一，育龄期早期卵巢上皮性癌患者保留生育功能治疗日益受到关注。文章对早期卵巢上皮性癌患者保留生育功能相关问题进行阐述。     

Her-2/neu expression and amplification in early stage ovarian surface epithelial neoplasms

OBJECTIVE: The aim of this study is to examine Her-2/neu gene amplification and protein overexpression in a spectrum of ovarian neoplasms using both immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) techniques that are FDA approved. This study is focused on early stage tumors including both carcinomas and borderline tumors. METHODS: FDA-approved IHC and FISH for Her-2/neu were performed on formalin-fixed, paraffin-embedded tissue from 79 ovarian neoplasms representing a broad spectrum of tumor types as well as four normal ovaries. All tumors were either stage I or stage II. Tumor and normal tissue were studied collectively using a tissue microarray (TMA). HercepTest (DAKO) and PathVysion Her-2/neu probe kit (Vysis Inc.) were used for IHC and FISH analysis. RESULTS: FISH analysis of serous carcinomas demonstrated Her-2/neu gene amplification in 3 (18%) of 17 cases. Two of three cases showing Her-2/neu gene amplification were scored 1+ using IHC, while the remaining case was scored as 0. Analysis of endometrioid carcinomas demonstrated Her-2/neu amplification using FISH in 1 of 10 (10%) cases. IHC in this case was scored 2+ (positive). None of the remaining 44 tumors, including clear cell carcinoma (n = 12), transitional cell carcinoma (n = 1), mixed epithelial carcinoma (n = 7), carcinoma not otherwise specified (n = 1), and 31 borderline tumors (mucinous, n = 17; endometrioid, n = 7; serous, n = 7), showed Her-2/neu gene amplification or protein overexpression. Normal ovaries were negative as well. CONCLUSIONS: Amplification of Her-2/neu in early stage ovarian neoplasms is infrequent, 6.7% overall. Due to the limited number of informative cases, we were unable to determine the clinical significance of Her-2/neu amplification in this study. Her-2/neu amplification was restricted to carcinomas and was not encountered in ovarian borderline tumors.     

The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas

OBJECTIVES: To examine the expressions of the protein and mRNA of EPHA2 and EphrinA-1 in epithelial ovarian carcinomas/ovarian cancer cell lines and explore their prognostic value. METHODS: To validate the immunohistochemical method, two ovarian cancer cell lines (OVCAR3 and SKOV3) were examined with RT-PCR, Western blot, and immunohistochemistry for EphA2 and EphrinA-1 expressions. Tumors from 118 patients with advanced epithelial ovarian cancer were then evaluated for EPHA2 and Ephrin A-1 protein expression, and frozen tissues from 30 cases were used for laser capture microdissection (LCM) assistant RT-PCR RNA analysis. RESULTS: 11 (9.3%), 67 (56.8%), 26 (22.0%), and 14 (11.9%) tumors demonstrated negative, weak, moderate, and strong EphA2 protein expressions, respectively, while 3 (2.5%), 67 (56.8%), 32 (27.1%), and 16 (13.8%) tumors were negative, weak, moderate, and strong for Ephrin A-1 protein expression, respectively. Variable amount of mRNA expression was observed in the 30 tumors analyzed by the method of LCM assistant RT-PCR. There was a trend for association between higher levels of either EphA2 or Ephrin A-1 expression and higher histological grade (P = 0.05 for both factors). No significant correlation between the expressions of EphA2 or Ephrin A-1 and age, histological type, and FIGO stage was observed. Patients with higher levels of EphA2 protein expressions had significantly shorter survival. Cox multivariate analyses revealed that residual tumor after surgery, histological type, and EphA2 protein expression were of independent prognostic significance. CONCLUSIONS: High level of EphA2 protein expression is significantly associated with a shorter patient survival and EphA2 receptor is a valuable prognostic marker for ovarian carcinoma.     

The role of cytoreductive surgery in the management of stage IV epithelial ovarian carcinoma.

Patients with Stage IV epithelial ovarian carcinoma are generally treated in the same manner as are patients with disease confined to the abdomen--cytoreductive surgery followed by combination chemotherapy. Between 1980 and 1990, 35 women with histologically or cytologically documented Stage IV ovarian carcinoma were treated in this fashion. Sixteen women (45%) underwent optimal initial cytoreductive surgery, defined as less than 2 cm maximum residual disease. Eleven of the 19 women undergoing suboptimal initial procedures underwent interval cytoreduction after two to four cycles of chemotherapy, with 7 achieving an optimal status after the interval procedure. Overall, 23 of 35 patients (66%) were successfully cytoreduced to less than 2 cm either initially or at an interval procedure. Thirty-one of the 35 patients received combination regimens containing platinum as part of their initial therapy. Kaplan-Meier survival curves demonstrated no significant difference in survival between those groups of women cytoreduced intervally or initially, or between those groups of women optimally cytoreduced at some point during their initial therapy and those who were not. The 5-year survival for the entire group was less than 5%, with no significantly prolonged survival seen in those patients undergoing successful cytoreduction.     

Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas

OBJECTIVES: To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN: Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS: Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION: Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.     

Surgery and prognosis in stage III epithelial ovarian cancer

The results of this retrospective case study indicate that a composite of tumor grade, pattern of spread and substage at the time of opening affects the outcome most in the treatment of stage III epithelial tumors of the ovary. The poorest prognosis was associated with grade 3 histology, a pattern of spread requiring extensive and often difficult surgery for removal and a high substage. The best prognosis was usually associated with grade 1, with either very easily removed, isolated spread or low substage.
The extent of tumor defined the degree of primary cytoreduction possible. If the tumor was minimally extensive, primary cytoreduction results were excellent. The same conclusions were reached in the case of secondary cytoreduction at the time of second-look procedure. There was no statistically significant difference ( z = 1.481, P = 0.069) in 5-year survival between patients with microscopic only disease (59%) at second-look, and patients with gross disease not cytoreduced (36%).     

Expression and clinical significance of apolipoprotein D in epithelial ovarian carcinomas

OBJECTIVE: Apolipoprotein D is a protein component of the human plasma lipid transport system but is also associated with a more favorable prognosis in women with breast cancer. This retrospective study was undertaken to examine the tumoral expression of apolipoprotein D in epithelial ovarian cancer and to analyze the possible correlation with tumor and patient characteristics as well as androgen receptors and their prognostic significance. METHODS: Immunohistochemical evaluation was used to examine apolipoprotein D expression in paraffin blocks from 68 epithelial ovarian carcinomas. RESULTS: A total of 18 (26.4%) tumors stained positively. No significant correlation was found between apolipoprotein D expression and patient or tumor characteristics and androgen receptor status. However, apolipoprotein D expression was significantly associated with prognosis in patients with residual tumor greater than 1 cm. Thus, patients with apolipoprotein-D-negative tumors had a poorer overall survival than those with apolipoprotein-D-positive tumors (P = 0.039). In addition, multivariate analysis demonstrated that apolipoprotein D expression was an independent prognostic factor with initial tumor size in this group of patients (P = 0.005). CONCLUSIONS: Our results led us to consider the existence of apolipoprotein D expression by a significative percentage of ovarian carcinomas, and this protein expression might be of clinical usefulness for identifying lesions with different evolution.