Level of estrogens and their metabolites in infected ovarian tissue in

advertisement

Level of estrogens and their metabolites in infected ovarian tissue in women having uterine carcinomas

T.I. Moiseenko , E.M. Frantsiyants , V.A. Bandovkina , E.F. Komarova , M.A. Vovkochina

Rostov Research Oncological Institute, Russia

ABSTRACT

1663

P

INTRODUCTION

15-20% of human neoplasms are currently supposed to have viral etiology. Hepatitis B and C virus, certain types of human papilloma virus and Epstein-Barr virus are found to have oncogenic effect. Liver cancer, cervical cancer, nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin lymphoma and some other tumors are the most frequent among virus-induced tumors [1].

There are data on intracellular infection of tumor tissues in different localizations of cancer [2]. Cancer modulation interaction of viruses with an existing tumor process results in increased tumor aggression, influence on cellular cycle of malignant cells, drug resistance, metastasis and neoangiogenesis increase.

Study of infectious agents' effect on changes in endocrine profile in hormonedependent and hormone-producing tissues during perimenopause can contribute to adequate choice of personalized treatments, identification of reproductive cancer risk groups and its prevention.

METHODS

Patients

 67 patients having uterine carcinoma T1-2N0M0 .

 Mean age 53 .

4 ± 3 .

2 years .

 Patients in perimenopause: menstrual dysfunction during 12 months.

Tissue Sample Analisys

 S amples of hystologically unchanged ovarian tissue, obtained during surgical treatment of patients with uterine carcinoma, were studied .

 H ormone level was defined in 10 % cytosolic fractions, prepared in 0 .

1 М potassium phosphate buffer рН 7 .

4, containing 0 .

1 % Tween-20 and 1 % bovine serum albumin .

 T he ELISA method was used to measure levels of estrone (E1), estradiol (E2), estriol

(E3) (XEMA, Russia) and 2-OHE 1 and 16αOHE1 estrogen metabolites (IBL,

International Gmbh, Germany) .

 O varian tissue infection with different viruses was detected by multiplex PCR with real-time hybridization-fluorescence detection of amplified products using Rotor-

Gene 6000 thermocycler (QIAGEN, Germany) .

 Intact ovarian tissue without IgG antibodies to infectious agents was used as the control.

Statistics

Statistical analysis of the results was made using Statistica program (version 8).

Student's t-test was used for confidence assessment. Written voluntary informed consent of patients was obtained in all cases.

THE HIGHEST PERCENTAGE OF INFECTION OF OVARIAN

TISSUE 35,8% WAS DETECTED IN THE COMPLEX OF

INFECTIONS CMV+HSV+CHLAMYDIA TRACHOMATIS

RESULTS

ESTRADIOL LEVEL DECREASES IN TISSUE OF UNLESIONED

OVARY OF UTERINE CARCINOMA PATIENTS WITH INFECTION

INFECTIONS DID NOT INFLUENCE CONCENTRATION OF FREE

ESTRIOL IN OVARIAN TISSUE OF UTERINE CARCINOMA PATIENTS

32.8% – HSV;

11.9% – CMV;

11.9%

CMV + HSV;

 7.6% – without infections.

without infections

CMV

HSV

CMV+HSV

CMV+HSV+Cl.trach

Frequency of infection in ovarian tissue of uterine carcinoma patients:

 35.8% – CMV+ HSV+ Chlamydia trachomatis;

ESTRONE LEVEL INCREASES IN TISSUE OF UNLESIONED

OVARY OF UTERINE CARCINOMA PATIENTS WITH INFECTION

CMV+HSV+Cl.trach

CMV+HSV

HSV

CMV without infections

CMV+HSV+Cl.trach

CMV+HSV

HSV

CMV without infections

0 200 400 600 800 1000 1200 1400

Estrone (pg/g of tissue)

 E

strone (E1) concentration was increased in tissue of infected ovaries by 1.6-3.5 times.

Hormone level increased to the maximum in HSV infection and exceeded the indices in other groups by 1.9 times on average.

CMV+HSV+Cl.trach

CMV+HSV

HSV

CMV without infections

Estriol (nm/g of tissue)

CMV+HSV+Cl.trach

CMV+HSV

HSV

CMV without infections

Estradiol (pg/g of tissue)

 Estradiol (E2) content in tissue of infected ovaries was decreased by

7

.

3-16

.

4 times on average in comparison with tissues without infections

.

 Estradiol (E2) level decreased to the maximum in patients with combination CMV+HSV.

RATIO OF 2-OHE1/16

Α

-OHE1 ESTROGEN METABOLITES IN

INFECTED OVARIAN TISSUE OF UTERINE CARCINOMA

PATIENTSWAS DECREASED BY 1,5 TIMES ON AVERAGE

Estriol (nm/g of tissue)

2-OHE1/16α-OHE1 ratio

Variation of 2-OHE1 and 16

α

-OHE1 metabolites ratio was associated with decreased content of 2-OHE1 and increase in the level of 16

α

-OHE1 in tissue of infected ovaries.

THE RATIO OF ESTRONE AND ESTRADIOL CONTENT

INCREASED SIGNIFICANTLY IN TISSUE OF UNLESIONED

OVARY OF UTERINE CARCINOMA PATIENTS WITH INFECTION

CMV+HSV+Cl.trach

CMV+HSV

HSV

CMV without infections

Estrone/Estradiol ratio

 Prevalence of E1/E2 ratio (by 25-28

.

8 times in comparison with noninfected) was maximal in HSV and in combination CMV+HSV

.

 In the rest cases: in CMV only and in its combination with chlamydia,

E1/E2 ratio increased by 15-16 times

.

CONCLUSIONS

Changing endocrine profile, infectious agents have a significant impact on the balance of estrogensz.

Ratio of estrogens changes towards estrone predominance if estradiol level is extremely low

REFERENCES

.

Ratio of metabolites of estrogens changes towards predominance of aggressive 16 α -OHE1

.

1. Gurtsevitch V.E. Human oncogenic viruses: from latent infection to tumor // Newsletter “Primary prevention of cancer”. 2006. № 1 (3).

2. Klochkova T.G., Evtushenko V.I. A role for human cytomegalovirus in definition of prostate cancer growth and aggressiveness //

Problems in oncology. 2012. Vol. 58. № 1. P. 33 40.

3. Cinatl JJr., Bittoova M., Margraf S. Cytomegalovirus infection decreases expression of thrombospondin-1 and -2 in cultured human retinalIglial cells: effects of antiviral agents // J. Infect. Dis.

2000. Vol. 182. P. 643 651.

Author’s email: super.gormon@yandex.ru

Download