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Santo Nicosia, MD

University of South Florida

Chair, College of Medicine, Pathology & Cell Biology University of South Florida

Basic research:
Our basic research focuses on the regulation of cell growth and morphogenesis in the ovarian surface epithelium (OSE), the source of the most frequent and lethal gynecologic malignancy. In particular, our laboratory is interested in the identification of genes and cytokines involved in the morphogenesis of ovarian papillary neoplasms. The underlying hypothesis of the research is that morphogenetic genes regulate transformation of OSE from a flat to a hierarchically branching papillary tissue. Using differential display, approximately 20 genes were discerned a few years ago that were either up-regulated (including microvascular endothelial differentiation gene) or down-regulated in rabbit OSE cells whose architecture had become predominantly papillary after 3 months of exposure to estrogens.

More recently using a DNA microarray approach, a number of angiogenic and epithelial morphogens have been identified as significantly upregulated or down-regulated in the papillary component of well-differentiated human ovarian serous cystadenocarcinomas. Among the upregulated genes were morphogens such as FGF18, FGFR-7, ephrins, Hox B7 and BMP7. Down-regulated genes included IGFBP5, thrombospondin, progesterone and androgen receptors as well as caldesmon.

We are currently in the process of setting up studies to investigate the functional implications of these genes in benign and neoplastic OSE cells via transfection and RNA silencing methodologies. Papillogenesis is also being reproduced in vitro utilizing heterotypic cultures of OSE cancer cells, endothelial cells and fibroblasts grown in collagen and basement membrane-rich matrices.

Translational research:
Previous studies have shown that OSE papillogenesis is stimulated by vascular endothelial growth factor (VEGF) and that VEGF is dramatically elevated in the cyst fluid of human ovarian papillary carcinomas consistent with the hypothesis that this cytokine may play an important role in ovarian cancer related-angiogenesis and tumor progression (1). Translating these results to the bedside, the laboratory has shown that seriousness of clinical status (OEC > benign lesions > healthy status) correlates with plasmatic VEGF, urinary scatter factor or HGF and urinary angiostatin. Angiostatin is the variable that independently discriminates OEC patients from volunteer controls and patients with benign ovarian masses. The diagnostic robustness of angiostatin as a screening or diagnostic tool in ovarian cancer needs to be explored further in a larger cohort of patients.

Clinical Research:
Recent trends toward conservative surgery for breast cancer and increasing detection of smaller invasive malignancies have shifted the traditional surgical approach from mastectomy to lumpectomy and from complete axillary lymph node dissection to sentinel lymph node biopsy in order to avoid extensive procedures in node-negative women. In collaboration with Dr. Charles Cox, we have developed imprint cytology procedures for the intraoperative analysis of lumpectomy margins and sentinel lymph nodes in breast cancer patients that allow for a rapid analysis of residual and metastatic disease without loss of diagnostic tissue and artifacts associated with pathological evaluation by the traditional frozen section method.

The Rivkin Center strives for excellence in our scientific programming. Our Scientific Advisory board guides the work we do and helps shape our vision for the future of ovarian cancer research. The Board is led by Dr. Mary L. (Nora) Disis, MD, our Scientific and Medical Director, and consists of nationally recognized experts in ovarian cancer research.


Talk to your Family

Talking to your family and identifying cancer in your family tree can be a good indicator of your health risks. Download our Family Tree Worksheet here.  Be sure to include yourself, children, parents, siblings, aunts, uncles, and grandparents.

Get Educated

Know your body and be proactive about your health. Learn about your breast and ovarian health. Learn about the risk factors and signs & symptoms for breast and ovarian cancer.

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Higher Risk in the Ashkenazi Jewish Population

In the general population, around 1 in 400 people carry a BRCA1 or BRCA2 mutation. People of Ashkenazi Jewish ancestry have a 1 in 40 chance of carrying a BRCA mutation, making them 10 times as likely to carry a BRCA mutation as someone in the general population. Whether you’re a man or a woman, if you have a BRCA mutation then there is a 50% chance of passing the mutation on to your children, whether they are boys or girls. It’s important to note that these mutations significantly increase risk, but are not a guarantee a person will get cancer.

Why is the Ashkenazi Jewish population at higher risk?

Over 90% of the BRCA mutations found in the Jewish community are one of three “founder mutations”. A founder mutation is a specific gene mutation in a population that was founded by a small group of ancestors that were geographically or culturally isolated. Because the population was isolated, the rate of founder mutations in descendants is much higher than it would be if the population were larger and co-mingling with more genetically diverse populations. A large expansion in the population caused the current high frequency of the mutations in the Ashkenazi Jewish population. If you are of Ashkenazi Jewish ancestry, the chance of carrying a BRCA gene mutation compared to the general population is increased tenfold. BRCA mutations can be passed down from either your mother’s or father’s side, and may be associated with any of the following cancers:
  • Breast cancer
  • Ovarian cancer, fallopian tube, peritoneal cancer
  • Male breast cancer
  • Prostate cancer
  • Pancreatic cancer
  • Colon Cancer

Ready to take action? Knowledge is power. Take this short quiz to be proactive about your health.

Genes 101

Our bodies are made of many tiny building blocks called cells. Our cells contain a copy of our genome – all of the DNA genetic code we inherited from our parents. Our genome is organized into 46 chromosomes, 23 inherited from mom and 23 from dad. Each chromosome has hundreds or thousands of genes. Each gene has the instructions to make a protein that may control the structure or function of cells, can determine many things including how tall we are or the color of our eyes. Genes also contain instructions for many things inside of us that we cannot see, such as how our bones are formed or how our heart works. Each gene is made up of molecules called nucleic acids (A, T, C, and G). The specific sequence of the nucleic acids holds the instructions that control all the components and their functions in cells.

If the DNA sequence is changed, like a spelling mistake, the instructions may not make sense. The technical term for this change is “mutation,” meaning there is a change to the usual genetic code that may change the instructions stored in the gene. A mutation in a gene that repairs DNA damage or controls cell growth can increase the risk of developing cancer.

Sporadic vs Hereditary Cancers:

Ovarian and breast cancer can be either sporadic or hereditary. Sporadic cancers make up the vast majority (85-90%) of ovarian and breast cancers and are not associated with family history of either cancer or inherited cancer-associated mutations. Sporadic cancers arise from genetic mutations acquired in some cells of the body by events part of normal metabolism and environmental factors. This type of cancer can happen to anyone. Most acquired gene mutations are not shared among relatives or passed on to children.

Hereditary (also known as inherited, or familial) cancers are those that occur due to genetic mutations that are inherited from mom or dad. Other blood relatives may also share these same gene mutations. Parents give one copy of each gene to their children. If a parent has a genetic mutation in a gene, each of their children have a 50% chance of inheriting that mutation. Therefore, even in families with hereditary cancer, not all family members inherit the mutation that is causing cancer, and their risk of cancer is similar to the average person in the general population. Individuals who are suspected to have a family history with high incidence of ovarian, breast, and other cancers may be offered genetic testing to try to find the specific genetic mutation that may put them at risk. Importantly, individuals who do not have a known genetic mutation but have high incidence of ovarian, breast, or other cancers in their families are still considered at higher risk for developing those cancers.

Hereditary cancers often occur at an earlier age than the sporadic form of the same cancer, so experts often recommend starting cancer screening at a younger age for individuals at high risk for hereditary cancer. Hereditary cancers can also be more aggressive than the sporadic form of the same cancer. Individuals who have inherited a gene mutation may be at a higher risk for more than one type of cancer.

BRCA 1 and BRCA 2: Most Common hereditary breast and ovarian cancer

The genes that are most commonly involved in hereditary breast and ovarian cancer (HBOC) are BRCA1 and BRCA2. These genes are named for their link to breast (BR) cancer (CA), but they are also linked to ovarian cancer risk as well as other cancers. Both women and men can inherit mutations in these HBOC genes. BRCA1 and BRCA2 are tumor suppressor genes that have a usual role in our body of providing instructions on repairing DNA damage and preventing cancer. When a family has an inherited mutation in BRCA1 or BRCA2, this leads to an increase in cancer risk. Not every man or woman who has inherited a mutation in the BRCA1 or BRCA2 gene will develop cancer, but people who have a mutation do have a significanlty increased chance of developing cancer, particularly cancer of the breasts or ovaries.

While breast and ovarian cancers are the most common cancers diagnosed in people with BRCA1 and BRCA2 mutations, the risk of some other cancers is also increased. Men with BRCA1 and BRCA2 mutations have a higher risk of early-onset prostate cancer than men without mutations in either gene. Other cancers seen at increased rates, particularly in individuals with BRCA2 mutations, include pancreatic cancer and melanoma. Researchers are continuing to find new genes that are involved in hereditary breast and/or ovarian cancer so it is important to follow up with a genetic counselor on a regular basis if hereditary breast and ovarian cancer is likely in your family.

Talk to your family about your health history and take the Assess Your Risk quiz here