Comprehensive allelotype study of ovarian tumors of low malignant potential: potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma.

Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors.     

Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR, alone and in combination, point to a favorable outcome for patients with OC.     

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case‐control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study‐specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow‐up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08–1.28) and former smokers (pHR = 1.10, 95% CI: 1.02–1.18) had worse survival compared with never smoking women. In histotype‐stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01–3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00–1.23; former smoking: pHR = 1.12, 95% CI: 1.04–1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.     

Epithelial ovarian carcinoma in the reproductive age group.

BACKGROUND: A retrospective review of women age < or = 40 years with epithelial ovarian carcinoma was undertaken to determine whether patient age and tumor grade are independent prognostic factors for survival, to investigate the survival rate for young women with ovarian carcinoma, and to characterize these young women in terms of reproductive capability. METHODS: The tumor registry of the Massachusetts General Hospital was used to identify cases of ovarian carcinoma diagnosed between January 1980 and July 1996. Patient records and pathology were reviewed. Survival rates were calculated by the Kaplan-Meier method and Cox proportional hazards models were used to determine the independent effect of each variable on survival. RESULTS: Ninety-two tumors epithelial tumors were identified with 46 (50%) classified as borderline. In the univariate analysis, stage (P < 0.001), grade (P < 0.001), residual disease (< or = 2 cm vs. > 2 cm, P < 0.001), and age (< 30 years vs. 31-40 years; P = 0.019) were found to be significant prognostic factors for survival. However, in the multivariate analysis only tumor grade (with borderline tumors assigned a grade of 0) and stage were significant predictors of survival (P < 0.01 for both). The 5-year survival rate for carcinoma patients with advanced disease was 22.9%. Patients with borderline tumors were more likely be diagnosed during an evaluation for infertility and were more likely to have successful live births after carcinoma treatment. CONCLUSIONS: Young women with advanced epithelial carcinoma have a 5-year survival rate similar to that quoted in the literature, despite the use of more aggressive chemotherapeutic regimens. Patients with borderline tumors of any stage have an excellent prognosis for preserving fertility options.     

Epidemiology of borderline ovarian tumors

Ovarian tumors of low malignant potential, often termed "borderline tumors," have been defined as those that have some but not all of the morphologic features of malignancy (i.e., they are not invasive). With the use of data obtained by the western Washington population-based Cancer Surveillance System for 1975-83, the incidence of serous and mucinous borderline epithelial ovarian tumors was analyzed, as well as the survival of women who developed them. The incidence of borderline tumors increased with increasing age, although at a pace somewhat slower than that of malignant ovarian tumors. There was an upward trend in the incidence of borderline tumors starting in the late 1970's, a trend not present for malignant tumors. Only 12% of borderline tumors were not confined to the ovary, as opposed to 40% of malignant Grade I and 73% of other malignant ovarian neoplasms. At 5 years following diagnosis, the survival of women with borderline tumors was 93% that of the general female population. This percentage varied little by stage or histologic type. Given the reduced survival of women with these ovarian tumors and the lack of a sharp histologic distinction between borderline and Grade I malignant lesions, it is recommended that borderline ovarian tumors be routinely ascertained by population-based cancer registries.     

Borderline ovarian tumors

Borderline ovarian tumors account for approximately 15% of all epithelial ovarian tumors. In the early 1970s, borderline tumors were categorized as either serous or mucinous with overall survival rates of 75–90%. Since then, it has been recognized that the two categories are heterogonous. There are now many different groups following the recognition of serous tumors with microinvasion, non‐invasive and invasive peritoneal implants and a micropapillary pattern, and of mucinous tumors with microinvasion, intraepithelial carcinoma and pseudomyxoma peritoneal implants, in addition to further delineation of endometrial, clear cell and transitional cell tumors with atypical proliferation. This review outlines the most recent information regarding the epidemiology, pathology and clinical management of borderline tumors. Surgical management to excise all visible tumors remains the cornerstone of therapy. Because borderline ovarian tumors often occur in reproductive‐age women, fertility is an important issue. Conservative surgery is a safe in carefully selected patients. Effective non‐surgical therapies are yet to be identified.     

年轻妇女卵巢上皮癌的临床特点及预后分析

背景与目的:卵巢上皮癌多发生于老年妇女,年轻妇女较少见.有关35岁以下妇女卵巢上皮癌的临床特点、预后因素分析报道较少.本研究旨在探讨年轻妇女卵巢上皮癌的临床特点、治疗、生存率及预后因素分析.方法:回顾性分析1980年1月至2003年12月我院收治的71例≤35岁的卵巢上皮癌患者的临床资料.生存率用寿命表法计算.利用Cox模型分析比较影响预后的因素.结果:71例确诊为卵巢上皮癌患者中位年龄28岁.临床表现为自扪及腹部包块或体检发现腹部包块18例,腹痛、腹胀各11例.肿物最大径平均为13.7 cm,肿瘤位于单侧52例(73.2%),68例(95.7%)行满意细胞减灭术,手术病理分期I期44例(62.O%)、Ⅱ期5例、Ⅲ期18例、Ⅳ期4例.病理类型以浆液性囊腺癌(40例,56.3%)和粘液性囊腺癌(22例,30.9%)为最多.病理分级为高分化42例(59.2%)、中分化18例(25.4%)、低分化11例(15.5%).68例术前或术后进行了以铂类和紫杉醇类为基础的化疗.15例保守手术中(均为I a、G1期患者),12例无瘤生存(80.0%).按寿命表法计算的2年生存率为86.0%.5年生存率为82.0%.Cox模型多因素分析显示病理分级、残留病灶大小是影响年轻妇女卵巢上皮癌预后的因素(P<0.05).结论:35岁以下妇女卵巢上皮癌患者,以单侧多见,以浆液性囊腺癌多见,预后好.部分I a、G1期患者可保留生育功能.病理分级、残留病灶大小是影响35岁以下妇女卵巢上皮癌预后的因素.     

Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years

BACKGROUND: Epithelial ovarian neoplasms are rare in patients under the age of 21 years. This is a report of a series of such patients documenting their presentation, histologic type, stage of disease, treatment, and outcome. METHODS: Clinical findings, histology, stage, treatment, and outcomes of 19 patients with epithelial ovarian neoplasia are reported. All histology was rereviewed. RESULTS: The median age at the time of diagnosis was 19.7 years (range, 14.1-21.8 years), and the median follow-up was 5.6 years (range, 0.2-19.5 years). The most common presenting symptom was dysmenorrhea (100%) followed by abdominal pain (68%), and the initial diagnosis usually was made ultrasonographically. There were nine (47%) serous tumors, 7 (37%) mucinous tumors, 2 (11%) small cell carcinomas, and 1 (5%) endometrioid carcinoma. Seventy-nine percent of tumors were unilateral, and 84% were low malignant potential or well differentiated tumors. Surgical treatment included unilateral salpingo-oophorectomy in 12 patients (63%), total abdominal hysterectomy and bilateral salpingo-oophorectomy in 6 patients (32%), and ovarian cystectomy in 1 patient (5%). Fifteen patients (79%) had Stage I disease, and 4 patients (21%) had Stage III disease at the time of diagnosis. There were two deaths in this series, and both occurred in patients with small cell anaplastic carcinoma. CONCLUSIONS: Epithelial ovarian neoplasias are rare in patients in this age group but must be included in the differential diagnosis of an ovarian mass. Most patients present with Stage I tumors of low malignant potential. In these patients, good survival is achieved with unilateral salpingo-oophorectomy and preservation of fertility. In contrast, small cell carcinomas are very aggressive, and patients with this variant require intensive therapy.     

Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas.

To investigate the potential role of the BCL-2 gene family (BAX, BCL-2, MCL-1, and BCL-XL) in ovarian cancer development and progression, mRNA expression levels of these genes were measured using semi-quantitative PCR in epithelial ovarian tumor tissues and normal ovaries. The immunohistochemical expression of MCL-1 in ovarian tumors was also examined. The expression levels of BAX and MCL-1 mRNA were significantly higher in ovarian cancers and in adenomas than in normal ovaries (P < 0.05). In contrast, the BCL-2 mRNA expression level in ovarian cancers was significantly lower than in ovarian adenomas and in normal ovaries (P < 0.05). Expression of BCL-XL mRNA was no different between normal ovaries and ovarian tumors. Log-rank testing showed that low BAX mRNA expression and high MCL-1 mRNA expression significantly correlate with poor survival for patients with stage III ovarian carcinomas (BAX, P = 0.05; MCL-1, P = 0.02). Immunohistochemical analysis showed that diffuse-positive expression of MCL-1 protein in mucinous carcinomas was significantly higher than in mucinous low malignant potential (LMP) tumors (P = 0.03). In ovarian cancer cases, diffuse-positive expression of MCL-1 protein significantly correlates with advanced clinical stage, high histologic grade, and poor survival (stage, P < 0.01; grade, P = 0.01; survival, P = 0.01). These results suggest that increased MCL-1 expression may play an important role in replacing the functions of increased BAX and decreased BCL-2 in ovarian carcinoma cells, thereby promoting cell survival, and resulting in a poor prognosis for patients with ovarian cancer.     

卵巢黏液性肿瘤中claudin-3、claudin-4的表达及其意义

目的 探讨claudin-3、-4在卵巢黏液性囊腺癌的发生、发展过程中的作用.方法 应用免疫组织化学、原位杂交方法检测卵巢上皮、黏液性囊腺瘤、交界性黏液性囊腺瘤、黏液性囊腺癌的石蜡包埋组织中claudin-3、-4和claudin-4 mRNA的表达情况.结果 claudin-3、-4、claudin-4 mRNA在卵巢上皮及卵巢黏液性囊腺瘤中表达最弱;交界性黏液囊腺瘤中表达明显增强,却明显弱于黏液性囊腺癌(P<0.05);在低分化卵巢癌中的表达强于高分化癌及中分化癌(P<0.05),中分化癌与高分化癌中的表达无统计学意义(P>0.05).结论 claudin-3、-4表达增强,与黏液性囊腺癌的发生、发展密切相关,与其分化程度有关,可能会成为诊断卵巢黏液性囊腺癌的特异性标记物.     

p53 expression, DNA ploidy and mitotic index as prognostic factors in patients with epithelial ovarian carcinoma

AIMS AND BACKGROUND: Biological variables linked to genomic instability were examined and related to survival in 52 patients affected by ovarian carcinoma and nine patients with low malignant potential tumors (LMP). METHODS: DNA ploidy was measured by image cytometry in isolated neoplastic cells; the mitotic index was measured in Feulgen-toluidine blue-stained sections and p53 was investigated by immunohistochemistry. RESULTS: Twenty-five tumors (4 LMP) were peridiploid (ploidy < 2.25c), 22 tumors (4 LMP) were hyperdiploid (2.25c > ploidy < 2.9c) and 14 (1 LMP) had high ploidy (> or = 2.9c). MI ranged from 0.3 to 24.2 with a mean of 1.8 for LMP and 6.8 for carcinomas (P<0.001). Widespread p53 overexpression was detected in 49% of carcinomas and in none of the LMP tumors. CONCLUSIONS: Survival analysis performed in patients with carcinomas indicated that, of the examined biological variables, only MI was moderately associated with survival in a subgroup of early-stage patients.     

Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Results from the SEER Program, 1978-1998

BACKGROUND: Malignant tumors of the ovary are the leading cause of death from gynecologic malignancies in the United States. Population-based incidence data for these neoplasms by histopathologic type and race are limited. Variation in rates may provide clues for future etiologic studies. METHODS: The authors performed a detailed, population-based analysis of U.S. incidence rates by histologic type, race, and age for invasive ovarian tumors that were diagnosed during 1978-1998 and for borderline ovarian tumors that were diagnosed during 1992-1998 using data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS: White women had significantly higher rates compared with black women of all types of epithelial tumors, with the white:black rate ratios ranging from 1.23 to 2.56. Black women had higher rates of gonadal stromal tumors. Among both white women and black women, total carcinoma rates did not change greatly from 1978-1982 to 1995-1998. Among white women, the reported incidence rates for invasive serous, endometrioid, and clear cell tumors increased during 1978-1998, whereas the rates of mucinous; papillary, not otherwise specified (NOS); and other epithelial tumors declined. Among black women, the reported rates of papillary, NOS tumors decreased significantly, whereas the rates of other tumor types fluctuated. Incidence rates of borderline ovarian tumors were higher among white women compared with black women and did not change significantly during 1992-1998. Serous and mucinous tumors were the predominant tumors reported for women age < 45 years, whereas serous; papillary, NOS; and other epithelial tumors predominated among older women. CONCLUSIONS: Incidence rates for malignant ovarian tumors have remained relatively stable, with higher rates for white women compared with black women. The reported rates for some specific histopathologic tumor types have changed over time, in part reflecting more specific pathologic classification. The possible effect of shifting exposure prevalence on incidence patterns warrants further study.     

间皮素mRNA及蛋白在卵巢癌中的表达及分析

目的 研究间皮素(MESO)在卵巢癌中的表达及意义.方法 用逆转录聚合酶链反应(RT-PCR)技术和免疫组化方法分别检测卵巢肿瘤和正常卵巢组织中MESO mRNA及其蛋白水平.结果MESO mRNA和蛋白在上皮性卵巢癌(1.4005 ±0.4646,2.7857±2.2712)和交界性卵巢肿瘤(1.0650 ±0.3100,2.9167 ±2.391)中的表达水平高于良性卵巢肿瘤(0.6463±0.2419,1.2500 ±1.6125)和正常卵巢组织(0.6439 ±0.2729,0.9167 ±1.2401),差异有统计学意义(P＜0.05);MESOmRNA和蛋白在浆液性卵巢癌(1.5255 ±0.4151,3.3036 ±2.6141)和子宫内膜样癌(1.5250 ±0.5419,3.0000 ±2.3094)中的表达水平高于黏液样癌(1.0675±0.3149,1.0556 ±1.9242),差异有统计学意义(P＜0.05);临床Ⅲ、Ⅳ期MESO表达水平(1.5100 ±0.4142,3.6087 ±3.3959)高于Ⅰ、Ⅱ期(1.1190 ±0.4909,1.7895 ±2.6320),差异有统计学意义(P＜0.05).MESO表达水平与病理分级有关(P＜0.05),而与患者年龄和血清CA125水平无关(P＞0.05).结论 MESO mRNA及蛋白在卵巢癌和交界性肿瘤组表达增高,MESO可能参与卵巢癌的黏附转移.     

Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study.

PURPOSE: Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS: All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS: We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION: The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.     

Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study

Population-based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow-up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 women with a BOT (2,058 serous BOTs and 2,223 mucinous BOTs) in Denmark during 1978–2012. We computed standardized incidence ratios (SIRs) to compare the incidence of ovarian cancer among women with BOTs compared to general population rates. We found that a serous BOT was especially and strongly associated with subsequent serous ovarian cancer (SIR = 9.2; 95% CI: 6.8–12.2), and that a mucinous BOT was strongly related to mucinous ovarian cancer (SIR = 18.6; 95% CI: 10.8–29.8). The SIRs remained elevated ≥10 years after a serous BOT and up to 5–9 years after a mucinous BOT. The increased incidence of serous ovarian cancer in women with a serous BOT was mostly pronounced in women <50 years at the serous BOT diagnosis. In conclusion, women with a serous BOT experience long-term increased incidence of serous ovarian cancer, and women with a mucinous BOT have long-term elevated incidence of mucinous ovarian cancer compared to the general population. This is the first population-based study to show compelling evidence of the histo-specific increased risk of ovarian cancer following specific types of BOTs. Thus, these results are supportive of the hypothesis that BOTs may be precursor lesions to carcinomas of the corresponding histologic type.     

Height, age at menarche, and risk of epithelial ovarian cancer.

OBJECTIVE: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels. METHODS: Participants were a population-based sample of women with incident ovarian cancer (n=794) and control women randomly selected from the Australian Electoral Roll (n=855). The women provided comprehensive reproductive and lifestyle data during a standard interview. RESULTS: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women>or=175 cm compared with women <160 cm, Ptrend=0.02). Similarly, later age at menarche was associated with increasing risk of mucinous borderline cancers (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at menarche>or=14 years compared with those <12 years, Ptrend=0.003). Women with mucinous borderline cancers were significantly younger than the women diagnosed with invasive cancers (mean 44 versus 57 years; P<0.0001). CONCLUSIONS: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.     

Update on low malignant potential ovarian tumors

Low malignant potential (LMP) ovarian tumors represent a small subset of epithelial ovarian cancers that were first identified 70 years ago but were recognized in a systematic way only within the last 30 years. These lesions afflict women at a much younger age than invasive ovarian cancer, behave in a more indolent manner, and have a much more favorable prognosis. The management of women with LMP tumors is primarily surgical; adjuvant therapy plays little role in early disease and its use in advanced disease is not well defined. Ongoing investigations are attempting to define prognostic factors that may assist clinicians in the appropriate application of postoperative therapy.     

Nuclear localization of phosphorylated ERK1 and ERK2 as markers for the progression of ovarian cancer

We examined the possibility that the localization of phosphorylated ERK1 and ERK2 (pERK1/2) can serve as a marker for the development of benign and borderline tumors as well as carcinoma of the ovary by an immunohistochemical method on ovarian paraffin sections, obtained from women aged 41-83 years. In normal tissue, 28.3% of nuclei were labeled, mainly confined to the epithelial cells at the surface of the ovary. In benign serous tumors, the label rose to 55.0%, while the intensity of the staining was weak. In contrast, in borderline serous tumors and in ovarian serous carcinoma (stage II) 52.1% and 70.3% of nuclei, respectively, were labeled with a high intensity. In mucinous benign tumors, the number of labeled nuclei was as in the control, but in addition, 49.4% of the cells demonstrated high concentration of pERK1/2 in aggregated form that was evident in the cytoplasm of the cells. In the mucinous and endometrioid ovarian carcinomas (stage II) very intensive labeling was found in 60% and 77.3% of cells, respectively. It is, therefore, suggested that since nuclear pERK1/2 can be mitogenic, it can serve as a reliable marker for the progression of ovarian cancer. Interestingly, the intense labeling of pERK1/2 was mainly confined to the peripheral areas of ovarian endometrioid carcinoma (stage II). In addition, all tumor cells in this class of cancer were positively stained with mutated p53. It seems, therefore, that immunohistochemical staining of normal and ovarian tumor cells with anti-pERK1/2 is a reliable marker for early detection of the cancer, which may assist in the early diagnosis and prognosis of this lethal disease.     

Endometrioid epithelial ovarian cancer : 20 years of prospectively collected data from a single center

BACKGROUND: Clinicopathological features and outcome of women with endometrioid and serous ovarian adenocarcinoma were compared. METHODS: Between 1984 and 2004, baseline and follow-up data were prospectively recorded on 1545 patients with ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous adenocarcinoma of the ovary. Response to platinum-based chemotherapy (PBC) overall survival, stage-for-stage median progression-free survival (PFS), and cause-specific median survival were compared. Independent predictors of survival were examined by using multivariate analyses. RESULTS: Median age of diagnosis for patients with endometrioid tumors was younger than those with serous adenocarcinoma of the ovary (60 years vs 62 years; P = .013). They presented more often with early disease (stage I and II; 50% vs 17%; P < .001), had less ascites, and had better performance status both overall and for stage II and III disease. More endometrioid tumors were optimally debulked overall (71% vs 45%; P < .001), but there was no difference according to stage. Objective and CA125 PBC response rates were not significantly different, but median PFS was better for patients with endometrioid tumors (24 months vs 13 months; P < .0001) as was overall median survival (48 months vs 22 months; P < .0001). This relation remained for stage II and III disease and for moderately and poorly differentiated tumors. Patients with concurrent endometrioid ovarian and endometrial malignancies had a survival advantage compared with those with ovarian malignancies alone. Independent predictors of survival after PBC were histological type, debulking status, and disease stage. CONCLUSIONS: Despite similar PBC response rates, endometrioid histology is associated with better survival compared with serous adenocarcinoma of the ovary, even with stage III or poorly differentiated tumors.     

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency questionnaires administered every 2 to 4 years starting in 1980. For the smoking analyses, 737 confirmed cases of epithelial ovarian cancer were identified and for the dietary aims, 507 cases were identified through June 1, 2004. RESULTS: Compared with never-smokers, neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors (n = 69; rate ratio [RR], past = 2.02 [95% confidence interval (CI), 1.15-3.55]; RR, current = 2.22 [95% CI, 1.16-4.24]). A modest inverse association between caffeine intake and ovarian cancer risk was observed (RR, top vs bottom quintile = 0.80; 95% CI, 0.60-1.07 [P = .03]), which was strongest for women who had never used either oral contraceptives (RR = 0.65; 95% CI, 0.46-0.92 [P for heterogeneity = .02]) or postmenopausal hormones (RR = 0.57; 95% CI, 0.36-0.91 [P for heterogeneity = .13]). Alcohol was not associated with ovarian cancer risk. CONCLUSIONS: The results of the current study suggest that cigarette smoking may only increase the risk for mucinous ovarian tumors, and alcohol intake was not associated with risk. However, an inverse association was observed between caffeine intake and ovarian cancer risk, particularly in women not using hormones; this finding merits further study.