Invasive and noninvasive implants in ovarian serous tumors of low malignant potential

Ovarian serous tumors of low malignant potential ("borderline" serous tumors) are classified according to the histologic features of the primary ovarian tumor, without regard to any coexisting extraovarian disease. The peritoneal implants display a range of histologic appearances, ranging from benign glands (endosalpingiosis), to noninvasive papillary glandular proliferations resembling the ovarian neoplasms, to irregular glands associated with a desmoplastic stroma and having features of invasive disease. This review of 16 patients with histologically documented extraovarian tumor implants seen at Indiana University Medical Center, Indianapolis, and 13 patients whose tumor implants have been previously described in the literature indicates that the clinical stage of disease has much greater prognostic significance than does the implant histologic features. There is a tendency for patients with more advanced disease to have invasive implants. However, within a given clinical stage, disease progression or recurrence was not influenced by the presence or absence of invasive histologic characteristics in the tumor implants.     

Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome

BACKGROUND:

Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown.

METHODS:

Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow‐up data were also analyzed.

RESULTS:

Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence.

CONCLUSIONS:

PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long‐term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.     

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.     

Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential

BACKGROUND: Methylation-mediated suppression of detoxification, DNA repair, and tumor suppressor genes has been implicated in cancer development and progression. Studies also have indicated that concordant methylation of multiple genes (methylator phenotypes), rather than a single gene, may predict cancer prognosis. The current study was designed to determine whether a methylator phenotype exists in ovarian cancer, whether methylation frequencies differ between malignant ovarian tumors and ovarian tumors with low malignant potential (LMP or borderline), and whether methylation of multiple genes affects patient survival. METHODS: The current study included 234 consecutively diagnosed patients with either LMP (n = 19 patients) or malignant (n = 215 patients) ovarian tumors. DNA samples were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin-like growth factor-binding protein 3 [IGFBP-3], glutathione S-transferase pi 1 [GSTP1], estrogen receptor-alpha [ER-alpha], and human MutL homologue 1 [hMLH1]) by using methylation-specific polymerase chain reaction analysis. RESULTS: The frequencies of methylation in malignant tumors and LMP tumors were 0% and 0% for GSTP1, respectively; 9% and 0% for hMLH1, respectively; 21% and 5% for BRCA1, respectively; 42% and 21% for p16, respectively; 44% and 26% for IGFBP-3, respectively; and 57% and 42% for ER-alpha, respectively. A methylator phenotype was not detected, but a calculated methylation index (MI) that was based on the total number of genes methylated in each tumor was associated with ovarian cancer risk and progression. A higher MI was associated with malignant tumors (odds ratio, 10.11; 95% confidence interval [95% CI], 1.19-85.75) and disease progression (hazards ratio, 6.53; 95% CI, 1.39-30.65). CONCLUSIONS: Although a methylator phenotype was not identified, the current results suggested that methylation of multiple genes may play an important role in ovarian cancer development and progression and may have clinical implications in prognosis.     

Stage I epithelial ovarian tumors of low malignant potential

Clinical and pathological details of 10 patients with stage I low malignant potential tumors of the ovary, between September, 1969, and February, 1988, have been reviewed. The mean age of the patients was 46.6 years. Six patients had serous and four had mucinous tumors. Of the 10 patients, five had a unilateral salpingo-oophorectomy, one had a bilateral salpingo-oophorectomy and four a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The mean duration of follow-up was 12.8 years. All patients have remained alive and disease-free. A recurrence occurred in one patient who has been managed well by additional surgery. Stage I ovarian tumor of low malignant potential appears to carry a favorable prognosis.     

Behaviour of ovarian tumors of low malignant potential treated with conservative surgery

Objective

Fertility-sparing surgery has been proposed for the treatment of borderline ovarian tumors. The aim of this study was to evaluate the outcome of patients submitted to cystectomy (CYS) compared with patients treated by unilateral salpingo-oophorectomy (USO) or bilateral salpingo-oophorectomy with/without total hysterectomy (radical surgery, RS).

Methods

We reviewed retrospectively the data of patients treated in 3 institutions for borderline ovarian tumors. One hundred and sixty-eight patients underwent laparoscopic or laparotomic surgical treatment from 1985 to 2006. Tumor recurrence rate, disease-free survival and site of recurrences were evaluated. Specific prognostic factors, such as stage, histology, micropapillary subtype, exophytic tumor growth, intraoperative spillage, endosalpingiosis, staging procedures, and route of surgery were analysed.

Results

Thirty-five patients underwent cystectomy, 50 unilateral salpingo-oopohorectomy, and 83 radical surgery. Twelve patients in the CYS group (34.3%), 10 in the USO group (20.0%), and 5 (6.0%) in RS group relapsed. Five-year progression-free survival (PFS) was 59.6%, 78.4%, and 93.5% in CYS, USO and RS groups, respectively. None of the relapsed patients died of disease.

Conclusions

Cystectomy is an effective surgical strategy for patients with borderline ovarian tumor. The higher risk of local relapses is not associated with a reduction in the overall survival. The procedure should be offered to young patients with bilateral tumors and to very young ones, considering the higher risk of local relapse.     

Ovarian tumors of low malignant potential

Opinion statement Ovarian tumors of low malignant potential (LMP) differ from epithelial ovarian carcinoma in etiology, molecular biology, and prognosis. LMP tumors are not precursor lesions to ovarian carcinoma. Treatment is primarily surgical. Women found to have an ovarian tumor of LMP should undergo removal of the involved adnexa; surgical staging; and cytoreductive surgery. Women in the reproductive years should be given the option of conservative surgery, preserving the contralateral adnexa and uterus. There is no proven benefit to adjuvant chemotherapy or radiotherapy after primary surgery. In most cases, the diagnosis of an ovarian tumor of LMP conveys good prognosis, with excellent long-term survival.     

Ovarian tumors of low malignant potential

Clinical and laboratory reports suggest that ovarian tumors of low malignant potential (LMP) represent a "grab bag" of tumors, with different etiologies, molecular biologies, and prognoses. As a result, data on incidence and prognosis may be quite unreliable. Diagnosis is best made on permanent section. Half of women under age 40 undergo conservative, fertility-sparing surgery when diagnosed with an ovarian tumor of LMP, but no adjuvant therapy has been shown to prolong survival in this population. In addition to the various controversies surrounding LMP tumors, this review will address prognostic markers, risk of malignant transformation, treatment of progressive disease, surveillance after conservative surgery, and future directions for research.     

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGbeta3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.     

Quantitative nuclear morphology in the diagnosis of ovarian tumors of low malignant potential (borderline)

Ovarian tumors of low malignant potential or of borderline malignancy are characterized histologically by the association of malignant type of epithelial proliferation with a noninvasive pattern of growth. Because epithelial proliferation relates to features of nuclear morphology and chromatin structure and because of the difficulties to distinguish nuclear atypism seen in borderline malignancy from that in frankly invasive tumors by usual microscopic study, the authors concentrated their studies exclusively on computerized analysis of cell nuclei images. Using specially developed methods of analysis the authors described geometrical, optical, and structural differences among the epithelial and stromal cell nuclei of benign, borderline, and malignant ovarian tumors. The structural differences concern the pattern of chromatin condensation and suggest that the cytokinetic properties of the borderline tumors are intermediate to those of benign and malignant. The results demonstrate that the quantitative evaluations provide objective and reproducible data useful in the differential diagnostic of the borderline malignancy.     

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.     

Clinico-pathological study of elderly women with malignant ovarian tumors

Twenty-five elderly women (those 70 years or older) with borderline and malignant ovarian tumors during the past 20 years were reviewed clinico-pathologically in comparison with 160 younger women (those 69 years or younger). The following results were obtained: 1) The incidence rate of elderly women for all patients of borderline and malignant ovarian tumors was 13.5%, and did not tend to increase in the past several years. 2) The rate that the elderly woman visited first at the other department excepting the department of obstetrics and gynecology was 36%, and which was statistically higher than that of the younger woman (p less than 0.01). 3) Fifty-two % of elderly patients had some complications and the incidence was significantly higher than that (23.1%) of younger patients (p less than 0.005). 4) Histopathologically in elderly patients, 9 patients (36%) were of serous cystadenocarcinoma and 17 patients (68%) were of malignant epithelial tumor (primary ovarian cancer and malignant Brenner tumor). 5) Of elderly patients, 8 (47.1%) were in Stage III and IV, and it was higher incidence than that (33.3%) of younger patients. In advanced cases, the histological grades became more poorly. 6) The survival rate of elderly patients in Stage III and IV was significantly lower than that in Stage I and II. The various treatment for Stage III and IV patients did not demonstrate the correlation in prognosis. In contrast, the survival rate for the group treated surgically in Stage I and II was significantly higher than that of non-surgical group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

卵巢恶性肿瘤相关危险因素分析

对３９６例卵巢包块病人进行回顾性分析，结果发现，恶性肿瘤６５例（１６％），良性肿瘤１５９例（４０％），子宫内膜异位囊肿１３０例（３３％），生理性囊肿２０例（５％），炎性包块７例（１％）。４０岁以上妇女卵巢恶性肿瘤的相对危险性显著增加（Ｐ〈０．００１），腹水、腹胀、泌尿道症状和体重，食欲降低是恶性肿瘤的重要危险因素。超声影像混合性包块与恶性肿瘤明显相关。     

Biotherapy of malignant peritoneal effusions in ovarian carcinoma

Malignant peritoneal effusions often arise in patients with ovarian carcinoma. They are a hazardous complication of cancer. Systematic intraperitoneal chemotherapy is not necessarily followed by long-term remission and may even induce untoward side effects. Intraperitoneal interleukin-2 (IL-2) and IL-2/lymphokine-activated killers (LAK) biotherapy showed high efficacy in treatment of ovarian carcinoma patients suffering from peritoneal effusions. The objective effect was 80.1% and 82.6%, respectively. Our results suggest that intraperitoneal biotherapy may be extended to dealing with malignant peritoneal effusions in ovarian carcinoma.     

Preoperative treatment with UFT for patients with ovarian malignant tumors

A 300-mg dose of UFT was administered daily for seven days prior to surgery for ovarian malignant tumors. The concentrations of FT, 5-FU and uracil in the serum, tumor tissue, adjacent normal tissue and ascitic fluid were measured. The results were as follows: 5-FU concentration in the serum was 0.008 +/- 0.006 micrograms/ml (n = 14) and the concentration in the ascitic fluid was 0.008 +/- 0.006 micrograms/ml (n = 4). The 5-FU concentration in the tumor tissue was 0.142 +/- 0.199 micrograms/g. This was approximately 3.0 times higher than the concentration in the adjacent normal tissue which was 0.048 +/- 0.030 micrograms/g and the T/B ratio (formula; see text) was approximately 17.8.     

A review of p53 expression and mutation in human benign,low malignant potential,and invasive epithelial ovarian tumors

BACKGROUND: In the current study, the authors present pooled data from studies that investigated p53 protein expression and/or mutation in human epithelial ovarian tumors. METHODS: The English literature in the MEDLINE, PubMed, and Ingenta databases was searched to the end of the year 2000 to identify relevant studies. Data were pooled across eligible studies, and the prevalence of p53 expression and mutation among benign, low malignant potential (LMP), and invasive tumors was determined. Prevalence estimates by tumor histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and grade also were calculated. RESULTS: The pooled prevalence estimate for p53 overexpression among epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50-53%) compared with 17% (95% CI, 15-20%) among LMP tumors and 7% (95% CI, 5-10%) among benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42-47%), 5% (95% CI, 2-9%), and 1% (95% CI, 0-5%), respectively, for invasive, LMP, and benign tumors. The prevalence of these p53 abnormalities was found to be associated positively with increasing tumor grade and stage. Differences based on histologic subtype also were found. CONCLUSIONS: Although these pooled estimates might appear to offer support for various hypotheses regarding the role of p53 in ovarian carcinoma, the limitations inherent in these data hamper the interpretation of the significance of any of the findings. Future studies will require innovative methods to address the limitations of many previous investigations and more comprehensive investigation into defective tumor suppression mechanisms.