Lykholat T.Yu.

National Dniepropetrovsk University by the name of Oles Gonchar

RECEPTOR STATUS AT MAMMARY GLAND CANCER

Oncology is a sphere of medicine and biology studying causes of origin, mechanisms of development and clinical displays of tumours. The oncology develops methods of diagnostics, treatment and preventive maintenance of tumours – excessive pathological growths of the tissues consisting of cells to an organism which have changed qualitatively and have lost differentiation.

Mammary gland cancer is a malignant tumour of a glandular tissue of a mammary gland. The causes of a mammary gland cancer following act factors: age, hormonal parameters, genetic factors, alimentary features etc.

The most effective diagnostics markers at mammary gland cancer are been: receptor of estrogens (ER), receptor of progesterone (PR) and HER - 2/neu is an epidermal factor of height.

Estrogens are a group of female sexual hormones which are synthesized in an organism by ovaries and regulate specific sexual functions. Excessive estrogens level in organism can become the cause of severity level various diseases at women (especially advanced age): it is capable to provoke a uterus and mammary gland cancer.

Estrogens receptor (ER). As receptors of other steroids estrogens receptor can be sectioned into some domains since the N-extremity. At mammary gland neoplasm estrogens receptors concentration has higher level than in a normal tissue [1].

Progesterone (gestagen) is a basic hormone of yellow body. Progesterone in a significant concentration secretes by a cortex of adrenals. It is the precursor in biosynthesis of glucocorticoids. Progesterone receptor is structured as other steroid hormones receptors. Progesterone influences on mammary gland epithelium proliferation, it can be used for an explanation of resistance gradually developing to the steroids in the processes of cancer progressing in the mammary gland [2].

HER - 2/neu (epidermal factor of height) is localized in 17q - chromosome and encodes tyrosine. It is kinase receptor of height factors. HER - 2/neu is gene of at epidermal height factor receptors family included EGFR or HER - 1 (erb - B1); HER - 2 (erb - B2); HER - 3 (erb - B3); HER - 4 (erb - B4). The gene amplification or HER - 2/neu protein expression meet at mammary gland cancer, tumours of lungs, gastroenteric tract, female sexual system and many other neoplasia. Its negative influence displays in stroma involving in receptors expression to the factor with the further "indirect" induction of tumour growth. Besides HER-2/neu expression plays an important role in prognosis and terms of occurrence of relapse at patients with metastasises [3].

The purpose of the presented work was studying the receptor status of the women suffered on a mammary gland cancer depending on this age.

Object of research were the mammary gland tissues specimens of the patients suffered on mammary gland oncologic diseases after operative measure. 350 specimens were researched.

An immunohistochemical method was used for studying of a cancer state. An immunohistochemistry (IHC) is a method of morphological diagnostics based on visualization and estimation with microscope results of an antigen-antibody reaction in the biopsy tissues specimens. The antigens are cellular structures components or tissue intercellular substance. Antibodies are received from blood serum of animals immunizated by an investigated antigen, or from culture of a tissue of a hybridoma framed by merge of "immortal" cells of plasmocyte tumour (myeloma) and the B-lymphocytes activated by an investigated antigen. Work was spent according to a technique of indirect step-by-step phase immunohistochemical research on system “Mouse/Rabbit Poly Vue HRP/DAB” [4].

At comparison of the investigated age groups of patients suffered on mammary gland cancer it is established that on estrogens receptor concentration quantity of the specimens with defined absence of a signal has noted as 29 %. The reaction in a range 1-100 was observed in 22 % of the specimens, 101-200 – 40 %, 201-300 – 9 % of the tissue specimens. On progesterone receptor concentration absence of the reaction is fixed in 34,5 % of the specimens. Force of a signal 1-100 was observed in 29 % of the investigated specimens, 101-200 – 26 %, 201-300 – 10,5 % tissue specimens. On epidermal factor of height expression level the group in which force of the reaction on expression Her-2/Neu was fixed as 0,1 + included 84 % of the surveyed patients, 2 + – 9 %, 3 + – 7 % of the patients.

At carrying out at the analysis on dependence the receptor status from the age factor following results are received. For group consisted by the patients at the age of 40-50 years, ER was absent in 41 % of the specimens, it was defined in a range 1-100 in 30 % of the cases, 101-200 – 26 %, 201-300 – in 3 % of the cases. Rather RG 42 % of the surveyed patients composed the group in which the signal was negative. In 28 % of cases force of the reaction was in limits 1-100, 101-200 – 20 %, 201-300 – 10 % of the investigated specimens, accordingly. Level of Her-2/Neu expression with force 0,1 + was observed at the majority of the surveyed patients (81 %), force 2 + – at 3 %, 3 + – 16 % of the patients.

For the group of the patients aged more 50 years such dependence is noted. The negative reaction on ER level was determined in 27 % of the specimens. The reaction in a range 1-100 was observed in 21 % of the tissue specimens, 101-200 – 41 %, 201-300 – 11 % of the investigated specimens. It isn’t noted the reaction on RG at 32 % of the specimens. Force of a signal in a range 1-100 is fixed in 30 % of the samples, 101-200 – 27 %, 201-300 – 11 % of tissue specimens. Force of Her-2/Neu expression as 0,1 + is observed at 90,5 % of the surveyed patients. It isn’t identified authentic differences between quantity of the patients with level of Her-2/Neu expression as 2 + (4,5 %) and 3 + (5 %).

Thus, the received results testify that with the age the risk of a mammary gland cancer beginning increases. The similar fact is defined by a metabolism change in the female organism that leads to hormonal status change, rising or depression of sensitivity level to endocrine therapy. At the same time metabolism rate depression causes to inhibition of proliferative growth of tumours. Behind the received data it is possible to assert that at women of the senior age group communication of estrogen with a corresponding receptor (ER +) is observed more often (73 % of cases) than at women at the age of 40-50 years (59 % of cases).

Approximately 76 % of mammary gland tissue primary tumours had the positive estrogen receptors status. The phenotype of tumours as ER +/PGR was more often defined at patients of advanced age. Her-2 amplification / hyperexpression directly correlated with the premenopause status and mammary gland tumour negative phenotype on estrogen level.

Reference:

1. Macaluso M., Montanari M., Giordano A. The regulation of ER-{alpha} transcription by pRb2/p130 in breast cancer // Ann. Oncol.- 2005.- № 4.- P.20-22.

2. Pasqualini J.R., Chetrite G.S. Recent insight on the control of enzymes involved in progestrogen formation and transformation in human breast cancer // J. Steroid. Biochem. Mol. Biol.- 2005.- Vol.93, № 2.- P.221-236.

3. Huang H.J. Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer / Huang H.J. // Clin. Pathol.- 2005.- Vol.58, № 6.- P.611-616.

4. Петров С.В., Райхлин Н.Т. Руководство по иммуногистохимической диагностике опухолей человека.- Казань, 2004. - 452 с.