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: (repost) Differences in tumor type in low-stage versus high-stage ovarian carcinomas

Int J Gynecol Pathol. 2010
Köbel M, Kalloger SE, Huntsman DG, Santos JL, Swenerton KD, Seidman JD, Gilks CB; Cheryl Brown (ovarian cancer survivour/deceased) Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency, Vancouver BC.
Department of Pathology, University of Calgary, Calgary AB, Canada T2N 2T9. martin.kobel@cls.ab.ca


Abstract

Although there are recognized differences in the type of ovarian carcinomas between those tumors diagnosed at low versus high stage, there is a lack of data on stage distribution of ovarian carcinomas diagnosed according to the current histopathologic criteria from large population-based cohorts. We reviewed full slide sets of 1009 cases of 2555 patients diagnosed with ovarian carcinoma that were referred to the British Columbia Cancer Agency over a 16-year period (1984 to 2000).
On the basis of the reviewed cases we extrapolated the distribution of tumor type in low-stage (I/II) and high-stage (III/IV) tumors. We then compared the frequencies with those seen in a large hospital practice.
The overall frequency of tumor types was as follows: high-grade serous-68.1%, clear-cell-12.2%, endometrioid-11.3%, mucinous-3.4%, low-grade serous-3.4%, rare types-1.6%. High-grade serous carcinomas accounted for 35.5% of stage I/II tumors and 87.7% of stage III/IV tumors.
In contrast, clear-cell (26.2% vs. 4.5%), endometrioid (26.6% vs. 2.5%), and mucinous (7.5% vs. 1.2%) carcinomas were relatively more common among the low-stage versus high-stage tumors.
This distribution was found to be very similar in 410 consecutive cases from the Washington Hospital Center. The distribution of ovarian carcinoma types differs significantly in patients with low-stage versus high-stage ovarian carcinoma when contemporary diagnostic criteria are used, with consistent results seen in 2 independent case series. These findings reflect important biological differences in the behavior of the major tumor types, with important clinical implications.

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

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."

full access: DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines

Table 1

Histology and clinical characteristics of primary ovarian tumors. (serous, endometrioid, clear cell - CA125 levels, menopausal status,patient age)

Background

Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood.

Clinical Presentation of Endometrioid Epithelial Ovarian Cancer with Concurrent Endometriosis: A Multicenter Retrospective Study — Cancer Epidemiology, Biomarkers & Prevention

Conclusions: In this large series of patients with EEOC, the main presenting symptoms were pelvic pain followed by gastrointestinal symptoms, palpable mass, abdominal distension, vaginal bleeding, and newly developed or exacerbated dysmenorrhea and dyspareunia. Dyspareunia and dysmenorrhea were more frequently detected in patients with endometriosis. Normal CA-125 levels cannot be applied as a marker to exclude EEOC, particularly at the early stages. Cancer Epidemiol Biomarkers Prev; 19(2); 398–404

The sensitivity and specificity of a new formula to distinguish endometrioid type endometrial carcinoma from ovarian endometrial carcinoma.(Japan)

Journal of Chemotherapy 2009 full access: What is the Benefit of 'Avastin' Combined with Chemotherapy in Patients - recurrent Ovarian, Primary ....

Journal of Chemotherapy 2009 full access: What is the Benefit of 'Avastin' Combined with Chemotherapy in Patients - recurrent Ovarian, Primary Peritoneal, Fallopian Tube Cancers.
Note: 64 patients in study; descriptive (stage 1C+); stage 1/11=4 pts; clear cell (2);endometrioid (3); mucinous (2);platinum resistant; side effects....(paper takes time to download)

Expression of interleukin-1 (IL-1) ligands system in the most common endometriosis-associated ovarian cancer subtypes

Note: highly technical paper comparing serous, clear cell and endometrioid ovarian cancer cells type/endometriosis/Interleukins (in research)

Abstract/full free access: Endometriosis-associated ovarian cancer: A ten-year cohort study of women living in the Estrie Region of Quebec, Canada

excerpts of interest: