Method for predicting the relapse of serous ovarian cancer

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with predicting the relapse of serous ovarian cancer after radical therapy before its clinical manifestation. The suggested innovation could be applied in daily practice of pathologoanatomic departments of hospitals, oncological dispensaries, specialized centers and research Institutes. The risk for the development of relapse is represented by a dichotomous variable calculated by the formula determined by logistic regression that includes the combination of several variables being morphological parameters of tumor, that is the area of tumor cell, average ploidy of tumor cells' nuclei, the level of p53 expression the level of expression of estrogen receptors, the level of PCNA expression. The innovation enables to predict repeated cancer growth according to morphological characteristics of primary tumor till clinical manifestation of the relapse.

EFFECT: higher accuracy and efficiency of prediction.

2 ex

 

The invention relates to medicine, namely to Oncology, and is intended for the diagnosis before clinical manifestation of recurrent serous ovarian cancer after radical treatment.

Known clinical predictor of early recurrence and/or metastasis of cervical cancer [1], based on the determination of the ratio of the absolute number of lymphocytes to the absolute number of peripheral blood monocytes with concomitant radiation therapy, followed by dividing the ratio by 4,05. When the values of the result above one say no probability of relapse within the first year of observation, while values below one ascertain the presence of continued tumor growth and recurrence of cancer in the first year after treatment. However, this method can only be used when cervical cancer and is not applicable to carcinomas other localization, in addition, the result does not reflect the degree of probability of a positive or negative result at the end of the year relapse-free period.

Also known is a method for predicting the recurrence of breast cancer [2], based on biochemical studies of menopausal patients after combined treatment. Relapse ascertain if the reduction ratio of the concentration of astria the and to the concentration of estrone and estradiol in urine depending on the duration of recurrence-free period. It should be noted that the method is applicable only when breast cancer in postmenopausal women and uses the parameters defined for biochemical analysis.

The closest method described in [3]. It lies in the fact that the forecast of development of recurrent endometrial cancer is set by the value of the ratio of cathepsin D and kislotostabilen inhibitors as determined by biochemical studies in tissue tumors, and endometrial. When the level of the coefficient is greater than the values typical for tissue intact endometrium, more than 2.4-2.8 times, predict the development of recurrence of endometrial cancer in the period up to 6 months.

The disadvantages of the method are the inability to use, ovarian cancer, prognostic judgment is not probabilistic in nature, and used options require specific biochemical methods.

The invention consists in that the forecast of the onset of relapse is established on the basis of the probability values calculated according to a formula determined using logistic regression. The formula is a combination of several variables, which is the morphological parameters of the tumor.

The technical result of the invention is the ability to forecast re-cancerous growth on morphologies the m characteristics of the primary tumor before the clinical onset of relapse, as well as the ability to use it when planning tactics of treatment of patients, as well as in the choice of treatment method.

The method is implemented as follows: define such parameters tumor size tumor cells, the average ploidy of the nuclei of tumor cells, the expression level of p53, the expression level of estrogen receptors, the expression level of PCNA.

The area of the cancer cell is measured by the eyepiece-micrometer or television image analyzer in μm2.

The average ploidy of the nuclei of tumor cells is measured by the photometer in units of the number of sets of chromosomes, C.

The magnitude of expression of p53 is expressed in points: the lack of p53 expression in tumor cells is scored 0; the expression of p53 detected in 1-10% of cells - 1 point; p53 is visualized in 11-50% of tumor cells - 2 points; p53 is defined in 51-100% of cancer cells is 3 points.

The level of expression of estrogen receptors was expressed in points: lack of expression of estrogen receptors in tumor cells is scored 0; the expression of estrogen receptors identified in 1-10% of cells - 1 point; estrogen receptors visualized in 11-50% of tumor cells - 2 points; estrogen receptors is determined in 51-100% of cancer cells is 3 points.

The magnitude of expression of PCNA (nuclear antigen of proliferating cells) is determined as a percentage of the number of PCNA - positive cells in the SDA is Oli.

Next, it calculates the probability of relapse according to the formula:

where X1 is the area of the cancer cell (μm2);

X2 - the average ploidy of the nuclei of tumor cells (C);

X3 - intensity labeling of p53 (in points);

X4 - intensity labeling of estrogen receptors (in points);

X5 - the value of the expression of PCNA (%).

While the final variable Y can take values in the range from 0 to 1. 0≤Y≤0,5 should be regarded as an indicator of low risk of resumption of tumor growth, while the 0.5≤Y≤1 testifies in favor of high risk of relapse.

The advantages of this method are the small number of morphological criteria, simplicity and low cost of the reagents to obtain the necessary parameters, the possibility of use in routine pathological practice and medical science. Examples of usage:

1. Patient M., 53 years of age, no history of the disease 4533, entered the Republican clinical Oncology dispensary mountains. Cheboksary September 25, 1998, in the direction of the precinct gynecologist. Upon receipt complained of heaviness in the lower abdomen, the increase in the abdomen. Heredity is not burdened, pregnancy was not. Objectively: the patient was in good condition, skin physiological painting,hemodynamic parameters within normal limits, vesicular breathing in lungs. Palpation of the abdomen is enlarged, soft, painless, during deep palpation by Obraztsov is determined by the free liquid in the abdominal cavity. At vaginal examination revealed a dense formation of granulomas in the pelvis on the left size of about 10 cm Pathological vaginal discharge no. Cytological examination of ascitic fluid in punctate Red space revealed atypical cells. Other changes in laboratory parameters are not set. At laparotomy diagnosed tumor of the left ovary solid character size 7 cm, capsule amazed. Produced hysterectomy with appendages and resection of the omentum with the following 6 courses of chemotherapy and hormonal therapy according to the standard scheme. Clinical diagnosis: Cancer of the left ovary, clinical stage Ic (FIGO), T1N0M0the ascites.

Histological examination was revealed serous histological type of carcinoma of the ovary with a low degree of histological differentiation. After conducting tsitomorfometricheskie study found that the average area of the tumor cells is equal to 82,35 μm. The average ploidy of the nuclei of tumor cells was 4,19 C. the expression of the antigen p53 was moderate (2 points), the expression level of PCNA - 70%, and the response to estrogen receptors weak (1 b the ll).

Thus, the calculated dichotomous variable Y:

Conclude that in this patient a very high risk of new cancer growth.

According to clinical observation of the patient obtained from the oncological dispensary, it is established that the patient M was diagnosed with a relapse of malignant neoplasms 9.04.2001 year.

2. Patient A., 58 years old, no history of 1598, came to the Republican clinical Oncology dispensary mountains. Cheboksary February 3, 1998, complaining of nagging abdominal pain, weakness. In anamnese 4 of pregnancy, heredity is not burdened. Objectively: the patient was in good condition, skin physiological painting, hemodynamic parameters in normal vesicular breathing in lungs. Palpation of the abdomen is enlarged, soft, painless, during deep palpation by Obraztsov is determined by the free liquid in the abdominal cavity. At vaginal examination in the area of the right epididymis diagnosed lumpy tumor site size up to 5 cm Pathological vaginal discharge no. When the puncture Red space in the peritoneal fluid revealed atypical cells. Other changes in laboratory parameters are not set. At laparotomy diagnosed tumor of the law is on solid ovarian character size 5 cm capsule amazed. Produced hysterectomy with appendages and resection of the omentum with the next 2 courses of chemotherapy and hormonal therapy according to the standard scheme. Clinical diagnosis: Cancer of the right ovary, clinical stage Ic (FIGO), T1N0M0the ascites.

Histological examination was revealed serous histological type of carcinoma of the ovary with a low degree of histological differentiation. After conducting tsitomorfometricheskie study found that the average area of the tumor cells is equal to 52,65 μm2. The average ploidy of the nuclei of tumor cells was 5,64 C. the expression of the antigen p53 - moderate (2 points), the expression level of PCNA - 100%, and the response to estrogen receptors high (3 points).

Thus, the calculated dichotomous variable Y:

Conclude that in this patient the risk of a relapse tumor growth is minimal.

According to clinical observation of the patient obtained from the Oncology center is established that the patient A. during the time of follow up relapse is not diagnosed.

Literature

1. The patent of Russian Federation №2247377 published 27.02.2005, Bulletin No. 6.

2. Application for invention No. 2003124101 published 27.01.2005, Bulletin No. 3.

3. The patent of Russian Federation №2250077, publish the consistent 20.04.2005, Bulletin No. 11.

A method for predicting the recurrence of serous ovarian cancer, which consists in the estimation of some parameters of the tumor and prognosis for him the possibility of recurrence of cancer, characterized in that it evaluated only morphological characteristics of the tumor and the likelihood of re-growth is determined by the formula

where X1 is the area of the cancer cell (μm), measured by the eyepiece-micrometer or television image analyzer, μm2;

X2 - the average ploidy of the nuclei of tumor cells (C) is measured by the photometer in units of the number of sets of chromosomes (C);

X3 - intensity labeling of p53 (point), the lack of p53 expression in tumor cells is scored 0; the expression of p53 detected in 1-10% of cells - 1 point; oncogene suppressor p53 is visualized in 11-50% of tumor cells - 2 points; p53 is defined in 51-100% of cancer cells - 3 points;

X4 - intensity labeling of estrogen receptors (point), no expression of progesterone receptor in tumor cells is scored 0; the expression of the progesterone receptor identified in 1-10% of cells 1 point; progesterone receptor visualized in 11-50% of tumor cells - 2 points; progesterone receptor is determined in 51-100% of cancer cells - 3 points;

X5 - the value of the expression of PCNA (nuclear ant the gene proliferating cells), %is determined by the number of PCNA - positive cells in the tumor, while the final variable Y can take values in the range from 0 to 1, 0≤Y≤0,5 should be regarded as an indicator of low risk of resumption of tumor growth, while the 0.5<Y≤1 testifies in favor of the high likelihood of recurrence.



 

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