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Clinical and Para-clinical findings of endometrial cancer with different expression level of biogenic amines


Author: Guţu Lilian
Degree:doctor of medicine
Speciality: 14.00.14 - Oncology and Radiotherapy
Year:2007
Scientific adviser: Dumitru Sofroni
doctor habilitat, professor, Public Medical Sanitary Intitution Institute of Oncology
Scientific consultant: Mihail Todiraş
doctor habilitat, associate professor (docent), State University of Medicine and Pharmacy "Nicolae Testemitanu"
Institution:
Scientific council:

Status

The thesis was presented on the 20 November, 2007
Approved by NCAA on the 20 December, 2007

Abstract

Adobe PDF document1.39 Mb / in romanian

Thesis

CZU 618.14-006.6-089-07

Adobe PDF document 1.90 Mb / in romanian
122 pages


Keywords

endometrial cancer, biogenic amines, serotonin, histology aggressiveness, vascular reactivity.

Summary

Endometrial cancer is the most common gynaecologic malignancy and accounts for 6% of all cancers in women occupying the 4-th place in the women’s cancer morbidity. Despite the fact that endometrial cancer is well studied oncology pathology from pathogenetic point of view, the inefficacy of prophylaxis and curative undertaken measures at this moment, dictates to look for new evaluations of genesis aspects of this illness.

This study tried to estimate the relationships between the two pathogenetic pathways of endometrial cancer and influence of biogenic amines synthesized in uterus, as well as their role played in the appreciation of evolution trough endometrial cancer aggressiveness.

There were investigated 232 endometrial cancer patients and 54 patients with benign uterine tumors. The results obtained using Ribonuclease protection assay, demonstrated that in more then 70% of endometrial cancer patients the level of mRNA for Tryptophan hydroxylase-1 (Tph-1), the initial and rate-limiting enzyme in the biosynthesis of the serotonin, was increased from 2 to 100 folds. The genetic level was confirmed by immunohistochemistry using monoclonal antibody for Tph-1. The positive staining for this enzyme was detected in tumor cells, but not in adjacent parenchyma.

A high level of messenger RNA for Tph-1 is a feature of endometrial cancer samples characterized by histological findings that obviously will suggest a more favorable prognostic. Paradoxical, in the tissue with elevated level of Tph-1 the level of serotonin was conversely, lowered. On the other hand, the tumor tissue characterized by a low level of Tph-1 the coupling of monoclonal antibody for serotonin was increased. The expression of estrogen and progesterone receptors allowed a better comprehension of tumor aggressiveness that correlated with the level of Tph-1 and serotonin. The histological findings showed that endometrial cancer tumors with a higher level of messenger RNA for Tph-1, a lowered one of serotonin and a diminished density of estrogen receptors were better differentiated and had a lower potential for growth.

Investigating in organ bath the vascular reactivity we demonstrated that such biogenic amines as noradrenalin, serotonin and histamine induced a more pronounced effects in the uterine artery rings extracted from patients with uterine cancer when the level of messenger RNA for Tph-1 in the tumour was lower. In patients with high level of messenger RNA for Tph-1, respectively the histological features of endometrial cancer tissue aggressiveness were lower and the contraction to noradrenalin and serotonin.

This study demonstrated role played by biogenic amines, especially by serotonin, in the pathogenic mechanisms and pro oncogenic changes in endometrial cancer genesis. The expression of mRNA level for Tph-1in tandem with standard morphology investigation can be used for appreciation of endometrial cancer aggressiveness and cancer treatment management.