Genetic studies by an international team of scientists have confirmed that the intractable endometrial cancer has four forms with varying degrees of drug susceptibility, which could not be determined by histopathological examination. The researchers also noted that the cancerous tumors of this type of cancer are the same as those of the hard-to-treat ovarian cancer and breast cancer. Thanks to these discoveries, it is soon possible to count on a reduction in the number of deaths caused by these cancers.
An international team of scientists from the USA, Canada, Norway, Finland and Our Country led by prof. Oncology, Douglas A. Levine of Memorial Sloan – Kettering Cancer Center in New York, made a significant discovery in the field of endometrial cancer research.
This type of cancer is the fourth most common malignant neoplasm in women. It is true that most cases occur in postmenopausal people, but more and more often younger women – aged just over 35 years – suffer from endometrial cancer. In the US, this cancer is considered the fourth most malignant – last year, 49500 new cases were detected, with 8200 fatal cases. In the USA and Western Europe, most of this type of cancer is detected at a relatively early stage, with small tumors. In Central Europe, diagnosis is usually later – cancerous tumors are usually already developed. The vast majority of patients with larger tumors can expect the spread of neoplastic lesions in the reproductive organs, and then throughout the body – in less than a year.
Until now, endometrial tumors have been classified into two types. The first of these has been commonly associated with obesity and excess estrogen. The prognosis for patients with this type of tumor was better than for patients with type II – serous, unrelated to estrogen stimulation, occurring in women of various body builds and usually slightly older. In the early stage of development of endometrial tumors, radiotherapy was usually used for type I, and for type II – chemotherapy, which was also used for both types of tumors at later stages of development.
Due to large differences in therapy, the tumors, despite having a similar picture and belonging to the same type, reacted differently to drugs. Researchers set out to perform transcriptomic, gnomic and proteomic analysis of several hundred samples from various types of tumors from 373 patients. 21 percent of the surveyed women recovered completely, 11 percent. died, the rest are struggling with the disease, usually in remission, but it cannot be clearly stated that the therapy has been completely successful and there will be no recurrence of cancer.
The results, published in the journal Nature, are sensational. It turned out that endometrial tumors can be divided into four subtypes with varying degrees of aggressiveness and chances of curing patients. The differences in individual subtypes concern somatic changes in gene copy number (SCNA), i.e. the multiplication of individual genes. It was relatively the smallest in the first subtype: patients with this cancer subtype had the best chance of full recovery. Most of the examined samples of endometrial tumors fell into subtypes 2 and 3, with patients with subtype 3 tumors having a lower chance of recovery than those with type 2 tumors. and MYC, which researchers have linked to the insensitivity of tumors to some basic chemotherapy drugs. This subtype can expect the relatively highest number of deaths in the 4 years from the time the sample was taken.
In further research, researchers found 48 genes with specific types of mutations that were different for each tumor subtype. The relatively highest number of major mutations occurred in subtype 4. Interestingly, the tumors did not differ at all in the currently most commonly used size and histological analysis. This means that the treatment of endometrial neoplasms must necessarily be combined with the genetic analysis of tumor samples.
As Prof. Maria Raeder from Universitetet i Bergen in Norway, the research broadens our understanding of endometrial cancer at the molecular level. According to the researcher, the fact that a new classification of tumors dependent on mutations has been developed provides new treatment options for patients with this type of disease and will certainly quickly reduce the mortality caused by this type of cancer.
Of course, this will not happen in 1-2 years, but will take about 5 years. As noted by prof. Oncology and Gynecology Sarah Temkin, working at the University of Maryland, more research is needed, this time on large series of samples, to confirm the findings so far. It is necessary to confirm and identify subtypes, especially in patients with poor prognosis, and to determine in which patients such prognosis should be expected, she stated in the description of the study.
Scientists are cautious because another, very important discovery was made during the work. During the previous work of an international team led by the oncologist prof. Christopher Benz from the University of California, it turned out that the forms of breast cancer that are difficult to treat and result in high mortality, known as triple negative (triple negative breast cancer – TNBC; it affects 2000 women annually in Poland), are very similar to ovarian and lung cancers . Until now, the dominant view was that each tumor is different at the molecular and genetic level, while an international research team consisting of researchers from the USA, Norway, Finland and Canada found after analyzing 20 different types of cancer that changes in this types found in different organs may be similar to each other.
The team of prof. Douglas A. Levine found a similar, significant relationship. It turned out that type II endometrial tumors, or serous, share the genome signature with ovarian serous tumors. These tumors account for about 40-50 percent. all malignant tumors of the ovary. They are mainly composed of cells of transformed surface epithelium. These cells fill cystic spaces of various sizes that line the solid or papillary structures. It is a late-recognizable cancer that is difficult to treat and may infiltrate adjacent organs and the peritoneum. These tumors are also very similar in genomic form to the difficult-to-treat TNBC breast tumors, which is related to the findings of the team of Prof. Benz. This discovery, as stated by prof. Levine, it is extremely important and requires some solid checking.
Confirmation of this discovery would mean that the moment is close when doctors, instead of histopathology of neoplastic tumors, especially in women, will perform genomic analyzes to determine what subtype they are dealing with, what the prognosis for the patient is and what type of therapy to use. This can significantly reduce the number of metastatic neoplasms and reduce the risk of dying from this type of neoplasm to a large extent. So it is a hope for a large number of women who may be affected by this condition.