How to follow up advanced-stage borderline tumours? Mode of diagnosis of recurrence in a large series stage II-III serous borderline tumours of the ov

BACKGROUND: The aim of this study was to describe how recurrences were diagnosed in the largest series of patients treated for an advanced-stage serous borderline ovarian tumour.
PATIENTS AND METHODS: From 1973 to 2006, 45 patients with a serous borderline tumour and peritoneal implants relapsed among 162 patients with a follow-up exceeding 1 year. Data concerning recurrences and the mode of diagnosis were reviewed.
CONCLUSIONS: This study demonstrates that ultrasound is the most relevant follow-up procedure in this context. Nevertheless, the blood CA 125 test is of particular interest for detecting invasive recurrent disease, which is the most crucial event.

abstract: (Aug 6, 2010) Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers

Blogger's Note: 

1) assumption - WAR (whole abdominal radiation - low dose/dosage; 2) ratio of cell types/RT; 3) study time period; 'apparent' stage 1/11; 4) surgical intervention by ?; 5) primary and/or secondary surgical debulking; 6) 'enhanced' as a %..... many questions in the absence of the full paper

 

Background: To explore the influence of ovarian cancer histotype on the effectiveness of adjuvant radiotherapy (RT).

Methods: A review of a population-based experience included all referred women with no reported macroscopic residuum following primary surgery who underwent adjuvant platin-based chemotherapy (CT), with or without sequential RT, and for whom it was possible to assign histotype according to the contemporary criteria.

Results: Seven hundred and three subjects were eligible, of these 351 received RT. For those with apparent stage I and II tumors, the cohort with clear cell (C), endometrioid (E), and mucinous (M) disease who additionally received RT exhibited a 40% reduction in disease-specific mortality and a 43% reduction in overall mortality.

Conclusions: The curability of those with stage I and II C-, E-, and M-type ovarian carcinomas was enhanced by RT-containing adjuvant therapy. This benefit did not extend to those with stage III or serous tumors. These findings necessitate reassessments of the role of RT and of the nonselective surgical and CT approaches that have characterized ovarian cancer care.

Prognostic Relevance of Uncommon Ovarian Histology (abstract) multinational study

 Note:   and stage 1/11??;  see abstract for authors

Prognostic Relevance of Uncommon Ovarian Histology in Women With Stage III/IV Epithelial Ovarian Cancer.

BACKGROUND::
The prognostic relevance of uncommon epithelial ovarian cancer (EOC) histological subtypes remains controversial. The Gynecologic Cancer InterGroup (GCIG) initiated this meta-analysis to assess the relative prognosis of women with a diagnosis of rare EOC histologies from completed, prospectively randomized studies performed by cooperative GCIG study groups.

METHODS::
Studies eligible for analysis included first-line treatment of at least 150 patients with stage III/IV EOC treated with a platinum/taxane-based regimen. Collaborating groups were to provide patient-level data. Serous acted as the reference histology, and a proportional hazards model was used to estimate the relative rate of progression or death.

RESULTS::
Data on 8704 women with stage III/IV EOC from 7 randomized trials were included in these analyses. Two hundred twenty-one patients (2.5%) had clear cell carcinoma; 264 (3.0%), mucinous; and 36 (0.4%), transitional cell. The mean age of patients with serous histology was greater than those with mucinous (4.1 years) and clear cell (2.6 years, P < 0.001). Mucinous, clear cell, and transitional cell tumors were more likely to be completely resected than serous (P < 0.05). When controlling for age and residual disease, mucinous and clear cell tumors had shorter times to progression (hazards ratio [HR], 2.1; 95% confidence interval [CI], 1.8-2.4 and HR, 1.6; 95% CI, 1.4-1.9, respectively) and death (HR, 2.7; 95% CI, 2.3-3.1 and HR, 2.2; 95% CI, 1.8-2.6, respectively) compared with serous. The median overall survival for serous, clear cell, mucinous, and endometrioid histologies were 40.8, 21.3, 14.6, and 50.9 months.

CONCLUSIONS:: Mucinous and clear cell carcinomas are independent predictors of poor prognosis in stage III/IV EOC. Studies targeting these rare histological subtypes are warranted and will require significant intergroup collaboration.

Abstract/full free access | Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival

Background

Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.

 Conclusions

AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.

"While several immunohistochemistry (IHC)-based studies have confirmed widespread AR (androgen receptor)expression in EOC, data describing it as a prognostic biomarker are relatively sparse. One study describing a large series of tumors (n=322), found no association between AR protein expression and clinical outcome, however individual histological subtypes were not examined. Increased levels of AR mRNA
have been described in cells from normal ovarian surface epithelium as compared to ovarian cancer cells, the majority of which were derived from serous tumors. We are, however, unaware of any studies describing AR expression in fallopian tubes, from which a substantial but not yet not fully appreciated proportion of serous ovarian carcinomas are thought to arise.."

The pathology of and controversial aspects of ovarian borderline tumours

Abstract
PURPOSE OF REVIEW: Ovarian borderline tumours are relatively uncommon, but not rare, neoplasms. Pathologists and oncologists often struggle with various aspects of borderline tumours which are sometimes controversial and poorly understood.

Functional Proteomic Analysis of Advanced Serous Ovarian Cancer Using Reverse Phase Protein Array: TGF-β Pathway Signaling Indicates Response to Primary chemotherapy

Abstract Purpose: Using reverse phase protein array, we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage, high-grade serous ovarian cancer. Conclusion: TGF-β pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted.

abstract/free full pdf access:P redictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies Cancers

"Abstract: Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer."
 ..........
"High grade serous tumors show particular differences in terms of their development, genetic alterations and prognosis. This has led to the classification of ovarian cancer into two types: type 1 tumors, which are low grade and slowly developing (endometrioid, mucinous and low grade serous tumors), and type 2 tumors, which rapidly progress (high grade serous). In addition, the association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. Although these data suggest substantial differences between subtypes, until recently ovarian carcinomas were typically approached as a monolithic entity by researchers and clinicians. This practice impeded progress in understanding the biology or improving the management of the less common ovarian carcinoma subtypes. To avoid this effect, each subtype within a cohort should be analyzed individually. Therefore, molecular classifiers of ovarian cancer are of high clinical relevance in the management of these cancer patients...." cont'd

Abstract / full free text: Expression signatures of TP53 mutations in serous ovarian cancers

Conclusions This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.

The origin of serous ovarian cancer may be found in the uterus: A novel hypothesis

full access: PLoS ONE: Ovarian Cyst Fluid of Serous Ovarian Tumors Contains Large Quantities of the Brain Amino Acid N-acetylaspartate

Background

"In humans, N-acetyl L-aspartate (NAA) has not been detected in other tissues than the brain. The physiological function of NAA is yet undefined. Recently, it has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation....."

full access: Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

Primary peritoneal cancer after bilateral salpingo-oophorectomy in two patients with Lynch syndrome.

Primary peritoneal cancer after bilateral salpingo-oophorectomy in two patients with Lynch syndrome.

Obstet Gynecol. 2010 Feb
Authors: Schmeler KM, Daniels MS, Soliman PT, Broaddus RR, Deavers MT, Vu TM, Chang GJ, Lu KH

BACKGROUND: Women with Lynch syndrome or hereditary nonpolyposis colorectal carcinoma (HNPCC) have a 40-60% lifetime risk of endometrial cancer and a 7-12% lifetime risk of ovarian cancer. Risk-reducing surgery, including hysterectomy and bilateral salpingo-oophorectomy (BSO), is currently recommended once child bearing is complete. We describe two cases of primary peritoneal cancer after BSO in women with Lynch syndrome or HNPCC.

CASES:
The first patient was a 44-year-old woman who underwent hysterectomy with BSO for benign disease. She presented 12 years later with a pelvic mass and was diagnosed with a high-grade serous primary peritoneal cancer. Genetic testing showed a mutation in the MSH2 DNA mismatch repair gene.
The second case was a 58-year-old woman who had a hysterectomy and BSO for endometrial cancer. She developed a high-grade serous primary peritoneal cancer 8 years later and was found to have a mutation in the PMS2 DNA mismatch repair gene.

CONCLUSION: Women with Lynch syndrome or HNPCC should be counseled that they may be at risk for developing primary peritoneal cancer despite undergoing gynecologic cancer risk-reducing surgery. The magnitude of this risk remains to be determined.

PMID: 20093870 [PubMed - in process]

Metastatic ovarian serous carcinoma presenting as inflammatory breast cancer: a case report.

Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

Note: in research/technical

Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms

Abstract

The HE4 protein is overexpressed in ovarian carcinomas and can be detected in serum by an ELISA with sensitivity similar to CA125 and higher specificity for malignant disease. We now demonstrate that HE4 can also be detected in the urine at a specificity level of 94.4%, including 13/15 (86.6%) with stage I/II and 57/64 (89.0%) with stage III/IV disease and including 90.5% of patients with serous ovarian carcinoma. Assaying serum and urine from the same patients showed similar sensitivity. Our data indicate that measuring HE4 in urine may aid diagnosis and the monitoring of response to therapy.

econdary Surgery in Patients With Serous Low Malignant Potential Ovarian Tumors With Peritoneal Implants

Conclusions: Secondary surgery seems to reduce the risk of recurrence in patients with serous LMPOT and peritoneal implants. Patients with residual disease are probably those likely to benefit from such surgery. Further studies are needed to confirm these preliminary results.

Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma

"The histopathological diagnosis of high-grade endometrioid and serous carcinoma of the ovary is poorly reproducible under the current morphology based classification system, especially for anaplastic, high-grade tumours.......In EOCs, WT1 protein is observed in the majority of serous carcinomas and in up to 30% of endometrioid carcinomas. It is unclear whether the latter is a reflection of the actual incidence of WT1 protein expression in endometrioid carcinomas, or whether a significant number of high-grade serous carcinomas have been misclassified as endometrioid carcinoma........It was found that nuclear WT1 protein expression can identify misclassified high-grade endometrioid carcinomas and these tumours should be reassigned to serous histotype. Although low-grade endometrioid carcinomas rarely progress to high-grade carcinomas, a combined WT1-negative, TP53-positive immunophenotype may identify an uncommon high-grade subtype of ovarian endometrioid carcinoma."

abstract/free full text: MicroRNA profiling of BRCA1/2 mutation-carrying and non-mutation-carrying high-grade serous carcinomas of ovary

CONCLUSIONS/SIGNIFICANCE: High grade serous ovarian carcinomas with and without BRCA1/2 abnormalities demonstrate very similar miRNA expression profiles. High grade serous carcinomas as a group exhibit significant miRNA dysregulation in comparison to tubal epithelium and the levels of miR-34c and miR-422b appear to be prognostically important. full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749450/?tool=pubmed

In Research: Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets (Japan)

In Research: 

Introduction:
Patients with advanced-stage ovarian cancer generally undergo primary debulking surgery followed by platinum/taxane-based chemotherapy. Although postoperative introduction of taxane drug has improved the 5-year survival rate for advanced-stage ovarian cancer..... Clinicopathological characteristics, such as debulking status after primary surgery, are clinically considered important indicators of prognosis. However, recurrence after optimal debulking surgery occurs in some patients, while disease-free status after incomplete surgery is maintained in others......Therefore, these clinicopathological factors alone are insufficient for predicting prognosis and elucidating the pathological mechanisms of disease progression or recurrence. Molecular biology approaches can be used to identify new prognosis-related profiles leading to elucidation of pathological issues of advanced-stage serous ovarian cancer.

Meanwhile, there are no microarray kits for clinical diagnosis and management in patients with ovarian cancer yet."

Molecular Profiling Uncovers a p53-Associated Role for MicroRNA-31 in Inhibiting the Proliferation of Serous Ovarian Carcinomas and Other Cancers

Note: miR-31 (rna/genome/gene)

"Our findings reveal that loss of miR-31 is associated with defects in the p53 pathway and functions in serous ovarian cancer and other cancers, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31."