Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features.

Abstract

Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and also the most lethal gynecological malignancies.
Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into five main types (high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous carcinomas (5%)) that account for over 95% of cases.

These types are essentially distinct diseases, as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, and molecular events during oncogenesis, response to chemotherapy, and prognosis. For a successful specific treatment, reproducible histopathological diagnosis of the tumor cell type is critical.

The five tumor types are morphologically diverse and resemble carcinomas of the uterus. Actually, recent investigations have demonstrated that a significant number of cancers, traditionally thought to be primary ovarian tumors (particularly serous, endometrioid, and clear cell carcinomas), originate in the fallopian tube and the endometrium and involve the ovary secondarily. This review summarizes recent advances in the molecular pathology which have greatly improved our understanding of the biology of ovarian carcinoma and are also relevant to patient management.

abstract: The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer (phase 1)

Purpose: This study evaluated the clinical relevance of the dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways.

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Experimental Design: We investigated safety, efficacy and correlations between tumor genetic alterations and clinical benefit in 236 patients with advanced cancers treated with phase I study drugs targeting PI3K and/or MAPK pathways in our Phase I Clinical Trials Program.

health media: BRCA1 Breast Cancer Risk Linked To Other Genes

"...People who carry certain mutations of the BRCA1 gene are known to have a higher risk of developing breast cancer.

Couch told the media that their findings should be "useful in helping determine individual risk for breast cancer in BRCA1 carriers".

"It also provides insights into hormone-receptor-negative breast cancer in the general population," he added.

For the study, Couch and colleagues conducted four phases of genome-wide association studies (GWAS) that altogether involved 20 research centers in 10 North American and European countries and Israel.

For the first phase, to identify candidate gene variants, they scanned the genomes of 1,193 carriers of BRCA1 mutations who were under 40 and had invasive breast cancer and compared them to scans of about the same number of controls: BRCA1 carriers of similar age who did not have breast cancer.

In comparing the genomes from the two populations the researchers examined over half a million genetic alterations. They found 96 pieces of DNA called SNPs, or "snips", short for single nucleotide polymorphisms, that they thought would be likely candidates because they differed between the two populations...."cont'd