Personalized diagnostics: Ovarian cancer

Ovarian cancer

Ovarian cancer mainly affects after menopause women-the majority of women diagnosed are over 50. Ranked seventh in frequency in women worldwide. The highest incidence of ovarian cancer is in Europe and North America and the lowest morbidity in Africa and Asia.

The most common type of ovarian carcinoma is called epithelial ovarian cancer and explains approximately 90% of all women with a diagnosis. Epithelial ovarian cancer begins in the ovarian epithelium - a thin layer of cells, covering the ovary or from the epithelium of the fallopian tubes.

Ovarian's non -exemplary cancer is relatively rare. Includes malignancies originating from germination cells, Stromal cells, Metastatic ovarian carcinomas and various extremely rare ovarian cancers, such as sarcomas and lipoid cell tumors. Non -expatriate malignancies represent about 10% of all ovarian cancers. The treatment of patients with tumors, originating from germinate cells is especially important, As most of them meet in younger persons, in which maintenance of fertility is important.

There are four basic subspecies of epithelial ovarian cancer

• Serosen cancer: This is the most common subtype, around 80% from the advanced ovarian carcinomas. They are divided into high -grade and low -grade tumors. Low -grade tumors represent approximately 10% from the serous subtypes, usually appear in younger women and are associated with a better prognosis;
• Mucinous: This subtype represents 7% –14% of all primary epithelial cancers of the ovaries. Diagnosed at an early stage, have a good forecast;
• Endometrioid: They are responsible for ovarian cancer at about 10% from women. Most of them are malignant and invasive. Usually, In imaging diagnostics are characterized as complex, non-specific hard-cistic. Are usually low -grade tumors, If diagnosed at an early stage;
• Light -cell cancer: This subtype carcinoma occurs at about 5% from the sick, But the percentage may vary depending on the population. The forecast for this subtype is pretty good, If diagnosed at an early stage of development. Light cell carcinoma is often associated with endometriosis, light -cell adenoff and light -cell atypical proliferative (Border) tumors;

Symptoms of epithelial ovarian cancer

In their early stages of development, Epithelial ovarian carcinoma may lead to slightly notable or missing symptoms, which makes it difficult to diagnose. More often his symptoms were observed in advanced illness. Signs, that can be observed, Regardless of the stage of disease development, include:

• Abdominal pain or pelvis;
• Vaginal bleeding;
• Constipation;
• Stomach;
• Diarrhea;
• Feeling of exceptional fatigue;
• Frequent need for urination;

While in advanced carcinoma:

• Abdominal circumference (Clothes may feel narrower);
• Bloating;
• Vomiting;
• Loss of appetite;
• Indigestion;
• Feeling of satiety shortly after starting a meal;
• Shortness of breath;

Possibilities

Based on symptoms, A medical or healthcare professional may suggest the presence of ovarian cancer and the need to perform research. Testing helps to determine the clinical (preliminary) stages. The clinical stage suggests the spread of the formation, which is relevant when applying surgery. The abdomen and pelvis examination helps to check that the organs are normal in size, Soft or hard or causing pain when touched. Your doctor will also feel the signs of fluid accumulation (ascites) in the abdomen or around the ovaries. Imaging methods will show location, size, the form of the tumor formation and whether it has spread outside the ovaries.

• Ultrasound – is often the first method used to seek ovarian cancer. Serves to assess the size, the shape and location of the ovaries, fallopian tubes, uterus and nearby fabrics. Can also show if there is a mass in the ovary and whether on the table is hard or full of liquid;
• CT (CT) – evaluated are well indicated whether the cancer has spread out of the ovaries. They can also show whether nearby lymph nodes are greater than normal, which may be a sign of its distribution;
• Nuclear magnetic resonance (NMR) - serves to evaluate signs of signs of cancer distribution. MRI does not use radiation;
• Positron emission tomography (Five) - CT or MRI is sometimes combined with five. In order to perform the study, it is necessary to inject intravenously safe radioactive chemical, called the sugar radiation, which serves to identify an oncological entity. Cancer cells look bright, because they metabolize sugar faster than healthy, normal cells. Five is very good at depicting small groups of cancer cells and can indicate whether ovarian cancer has spread;
• Radiography – The X -ray can indicate whether the cancer has spread to other organs, like the lungs. Can be combined with other studies with initial suspected ovarian carcinoma or serve to track the results of the treatment performed. Chest radiography is fast and painless and uses small amounts of radiation;

In advanced ovarian carcinoma, Diagnostic laparoscopy may be required before treatment of treatment. The method represents a minimally invasive procedure, чиито резултати помагат при взимане на решение дали операцията да бъде предприета като първоначално лечение или ако е необходимо прилагане на неоадювантна химиотерапия.

When diagnosing ovarian cancer, tissue sample (biopsy) should be separated from your body to test. Biopsy was usually done during the initial tumor removal surgery. But sometimes it's done, To diagnose ovarian cancer before surgery or other planned treatment.

Family history and genetic testing

In- much of the cases, Ovarian cancer occurs sporadically for an unknown reason. However, about 1 from 6 The ovarian cancer is caused by mutations (changes) in genes, which are transmitted by a parent to a child. This is called hereditary ovarian cancer. Most often caused by mutations in Krca1 and BRCA2 the genes. Each of us is the carrier of these two genes, that help repair damaged cells. In the event of violations and mutations in Krca1 and BRCA2 the genes, increases the risk of ovarian carcinoma occurrence, breast and some other types of malignancy.

Another cause of hereditary ovarian cancer is Lynch syndrome (Lynch syndrome). Lynch syndrome is a common cause of hereditary cancer of the colon and uterus, But it can also lead to ovarian cancer and other cancers. Ovarian cancer, consequence BRCA mutation or lynch syndrome, may occur at a younger age compared to the inquiring form of ovarian cancer.

On the basis of age, Health and Family History, A medical specialist assesses the likelihood of hereditary form of ovarian carcinoma. Genetic examination can help to understand if there is a mutation in a mutation in BRCA genes or in other cancer-linked genes and is recommended for everyone with family burden, diagnosed with ovarian cancer. If the initial treatment works well, BRCA testing, regardless of its status (a positive or negative result) play an important role in making therapeutic decisions. Genetic testing requires a small amount of venous blood or sample rubbing from a buccal mucosa (the inside of the cheek). Persons with a positive genetic test or who have a strong family cancer, You should visit a healthcare professional and it is recommended to conduct a genetic counseling. In addition to testing for hereditary BRCA mutations, A sample testing may be recommended by the tumor itself. Mutations, found in the tumor formation are known as somatic or tumor mutations.

Genetic examination is recommended for all diagnosed with ovarian cancer. It can determine if you have a mutation in BRCA genes or in others, who play a role in hereditary cancer.

Biomarkers

• Tumor markers – represents a substance, found in body tissues or fluid, which may be a sign of cancer. Tumor markers examination is not used alone to diagnose oncological disease, But their changed serum levels can signal for health problems. Along with other information, Tumor markers can help diagnose ovarian cancer and track the answer to treatment.

Cancer antigen-125 (CA-125) is the most commonly tested ovarian cancer marker. It should be considered, that healthy states, which are not oncological, such as endometriosis and diverticulitis, can also raise levels of CA-125. Also not always low levels of CA-125 are associated with the absence of ovarian carcinoma. Some types of ovarian cancer do not lead to an increase in CA-125.

In individuals with less common ovarian carcinoma, can be aimed at testing other tumor markers.

• Inhibit (usually inhibin A and inhibin in) -Combined with CA-125, Helps evaluate the presence of cancer and also diagnose an ovarian tumor, called a granulosa cell tumor, and is less commonly used to diagnose mucinous epithelial tumor of the ovaries;
• Beta-human chorionicgonadotropin (β-hCG) - Increased values ​​can be observed in young women with tumors of germinate ovarian cells;
• Alfa-Fetoprotein (AFP) - Also associated with tumors of the germinate cells of the ovaries;
• Lactate dehydrogenase (LDH) – Combining Serum LDH with other tumor markers such as alpha-phyetoprotein, CA125 and HCG-β improves the diagnosis of certain types of ovarian tumor;
• Carcinoemboline antigen (CEA) -in combination with CA-125 can improve diagnosis;
• CA 19-9 – the high levels of ca 19-9 are associated with some types of ovarian cancer, including light cell cancer, teratomas and secondary malignancies;
• HE4 – human epididyamis protein 4 (HE4) is used in conjunction with CA-125 to monitor women, who have been treated for epithelial ovarian cancer;

Genetic markers (biomarkers)

Biomarkers are taming hackers, that can help refer to appropriate treatment (tumor profiling). Often represent mutations (changes) In the DNA of Cancer Cells. Biomarker testing involves analyzing a small amount of tumor tissue or a blood test examination in certified and accredited, A highly specialized and technology laboratory, Next practices of good laboratory work (GLP). In addition to choosing a specific maintenance therapy, Results can direct to appropriate clinical trials.

BRCA mutation is one of the most important biomarkers, used to predict and predict in ovarian cancer. BRCA Mutations are a form of homologous recombination deficiency or so -called HRD – status. But HRD - a positive status can be observed with other changes in DNA, who are also relevant to disease treatment.

• Microsatelite instability (MSI) – represents a genetic change, which may occur in some types of ovarian cancer. This is happening, When the body's normal process to correct small DNA errors do not work properly. As a result, small repetitive areas of DNA, called microsatellites, become unstable or change their length. The presence of MSI in ovarian cancer can affect the behavior of the disease and how it responds to certain treatments. For example, MSI tumors often respond better to specific immunotherapy drugs, that help the immune system recognize and attack cancer cells. MSI testing helps medical professionals better understand tumor characteristics and the ability to target personalized therapies;
• Correction (MMR) - is a natural process in cells, that helps correct small DNA errors - instructions, who tell your cells how to grow and function. In some cases, the MMR system does not work properly or so -called "MMR deficiency" leads to changes or the occurrence of mutations in DNA. This may increase the risk of developing certain types of cancer, including ovarian cancer. MMR status testing is important, Because helps doctors better understand your specific cancer. The positive result for MMR deficiency, can aim to choosing a more appropriate and personalized therapy;
• Her2 expression – Her2 is a protein, found on the surface of some cancer cells, including some types of ovarian cancer. When ovarian cancer cells have high levels of Her2, This can sometimes make cancer more aggressive. HER2 testing helps to make appropriate therapeutic decisions;
• Tumor mutation (TMB) – Refers to the number of genetic mutations, found in the tumor. In ovarian cancer, TMB study will help doctors understand how cancer can respond to certain treatments, especially immunotherapy. Higher TMB means, that there are more mutations in cancer cells, that can make the tumor more recognizable about the immune system. This can potentially lead to better therapeutic answers, that help the immune system fight cancer. Backwardly, A lower TMB can mean, that the tumor is less likely to respond to these types of therapies;

Braf v600e mutation – represents a specific change or mutation in a gene, called BRAF. The presence of BRAF V600E, may cause cells to grow and divide faster, than, which can contribute to the development of cancer. This mutation is less common, but it is important, because it can affect the behavior of the disease, the choice of and the answer to certain treatments. In particular in low-stage serous ovarian cancer and border serous tumors, BRAF V600E is associated with a more favorable prognosis and potential sensitivity to BRAF inhibitors therapies. This mutation is also associated with an early stage of the disease and serous border histology;

• Expression of folate receptor alpha (FRα) - is often over -exposed and connected to the aggressiveness of the tumor, resistance to chemotherapy and worse results. Frα is a protein on the cell surface, that plays a role in cell growth and division;
• Ret mutations – have been identified in some epithelial ovarian cancers. These mutations can lead to stimulation of cellular growth and cell survival. It is important to establish, that mutations in the RET gene are associated with the application of appropriate targeted therapies;
• NTRK gene merge -They meet less often, But their presence can direct the choice of appropriate targeted or inhibitory therapies, especially in advanced, recurrent or resistant treatment cases.

If you have questions about the study of biomarkers or appropriate ones, Remember to discuss them with your health team.

Prepared: Silva Kurkchian, dB

Sources:

• National Cancer Comprehensive Network (National Comprehensive Cancer Network): https://www.nccn.org
• European Society of Medical Oncology (European Society for Medical Oncology): https://www.esmo.org
• National Center for Biotechnological Information (National Center for Biotechnology Information): https://www.ncbi.nlm.nih.gov