PROGRESSION OF THE TUMOUR (Latin progressio advance, growth) — process of emergence and the subsequent strengthening of qualitative characters of a tumor — autonomy of growth, invasiveness, ability to innidiation, etc. Symptoms of a malignant tumor develop independently one from another, forming various combinations. Time of manifestation of each sign can vary over a wide range.
The concept about P. the lake through discontinuous variations as a part of neoplastic population was developed by F. Raus (since 1935 but 1950) on the basis of researches of the papilloma of Shoup turning under certain conditions into a carcinoma. Finally formulated P.'s concept of the lake Foulds (L. Foulds, from 1949 to 1969). He noted that females of rats of the high-cancer line at each new pregnancy had a tumor of a mammary gland. The first of them was absolutely hormonedependent and disappeared after the birth of cubs, the subsequent tumors gradually lost a gormonozavisimost and continued to develop freely at a nonpregnant animal. It is explained by the fact that every time after a rassasyvaniye of a tumor the small group of its cells possessing a potential gormononezavisimost survived and then turned into the prevailing population creating a new tumor. According to Foulds, malignant new growths with the growth and development undergo a number of irreversible changes; the progression in the different centers of a multiple tumor is made independently, also independently there is also a change of properties in different sites of the same tumor.
Foulds's position about independence of symptoms of a malignant tumor was added with idea of their non-equivalence. Allocate primary, radical, the sign, the general for all new growths, both high-quality, and malignant, is an uncontrollable growth (see. Autonomous growth). Besides, there are secondary signs arising during P. of the lake. They are subdivided into development of this malignizirovanny fabric, obligatory for all stages (infiltrative and destructive growth, systemic action on an organism) and optional (a cataplasia, ability to innidiation, chromosomal anomalies, etc.).
Studying of hemoblastoses of the person allowed to open some mechanisms which are the cornerstone of P. of the lake and a carcinogenesis in general (see. Carcinogenesis ). First of all the klopovy basis of hemoblastoses was proved, i.e. it was established that these tumors consist of cellular posterity — a clone — one originally changed cell. The clone coming from initially transformed cell, phenotypical gomogenen. However in process of development of the tumoral center the increased genetic variability of its cells begins to affect, and population becomes heterogeneous on the properties. In an organism there is a natural selection of cells, more autonomous and resistant to the regulating influences, and also to cytostatic drugs. From the cells having similar properties new subclones with the raised zlokachestvennost expand, and it repeatedly repeats.
A pilot model of this process are experiments on introduction to blood to mice of cells of a mouse melanoma. Part of these cells formed tumoral nodes in lungs; such clones selected, again transferred to culture and then repeatedly entered into blood an animal. After 10 such passages the selected clones gained repeatedly increased ability to innidiation in comparison with a stock culture.
An indispensable condition of P. of the lake is proliferation. E.g., the methylcobalamine having mitogenetic properties and stimulating proliferation of tumor cells increases the frequency of emergence at the animal malignant tumors induced p-oxyphenyl-lactic to - that.
The metastatic tumoral centers can represent the new qualitative options of the main tumor differing both on intensity of proliferation and aggression, and on sensitivity to cytotoxic influences. So, metastasises in a cover of a head and spinal cord at leukoses resolve after introduction to the spinal channel of a methotrexate in combination with arabinozidtsitoziny. while the basic tumoral process in marrow is resistant to these drugs.
During the studying of tumors of the person their heterogeneity at a stage of generalization both in the relation to cytostatic influences, and on ability to new changes, i.e. a progression is established. Studying of a lymphogranulomatosis, lymphosarcomas, leukoses showed that clinically definable primary center of defeat is the most probable source of a palindromia after its successful treatment. It is the center of the most probable emergence of new clones of tumor cells while, e.g., the metastasis in a cover of a brain even in case of a repeated recurrence for years does not find signs of innidiation out of limits of covers of a brain, signs of a progression, edges would be expressed in emergence of stability to earlier effective cytostatic drugs. From these observations the conclusion was drawn on need of radiation of primary centers of a lymphogranulomatosis for higher doses, than zones of visible and estimated innidiation.
It is also noted that while the monoklonovost hron remains, a myeloleukemia, an erythremia, hron, a subleukemic myelosis, their progression is not found. During this period they are morphologically stable and remain sensitive to the same drugs. As soon as there are subclones revealed, in particular, on chromosomal markers quickly resistance to earlier effective therapy increases, the cellular differentiation is broken, the cellular atipizm appears — the tumor from high-quality turns into malignant.
The hyperplastic proliferating centers and benign tumors can be the first stages of P. of the lake. At an experimental carcinogenesis in skin, a mammary gland, a uterus, a stomach and lungs it is possible to observe direct transitions from the hyperplastic centers to more atipichesky populations of cells having symptoms of a malignant tumor. They often arise multitsentrichno, but each such center representing in most cases posterity of one cell can be at different stages of P. of the lake. It is possible to observe similar natural changes at patients, e.g., at adenomas of bronchial tubes, proliferative mastopathies with transition to adenoma and further in invasive cancer, and also at emergence of multiple polyps and hereditary adenomatosis of a large intestine, maligniziruyushchikhsya sometimes to 100% of cases. Also long absence of infiltriruyushchy growth and innidiation at already accurately expressed atypia of structure is possible. Benign tumors which populations of cells progress seldom are known or never progress or even regressions can be exposed.
Gistol. features of tumors change in the course of their growth too, testifying to P. the lake. So, the tumors keeping to some extent a structure of initial body, napr of an adenocarcinoma, are transformed to the tumors deprived of these structures. During a progression malignant new growths can lose and biochemical, the characteristics inherent in homologous normal fabric.
Along with P. the lake did not exclude also a possibility of regression. It is often observed in the hyperplastic proliferative centers, is more rare at benign tumors and by way of exception — at malignant new growths. There is an assumption that jumps of conditions of the environment are the reason of regression, in a cut clones of the corresponding cells grow that leads to the stabilizing selection to a stop of proliferation. Not numerous cases of reversion of malignant tumors (i.e. the return P.'s process by the lake), in particular neuroblastomas at children are described.
Bibliography: Bogovsky P. A. Morphological manifestations of a progression of tumors, Arkh. patol., t. 44, century 2, page 3, 1982, bibliogr.; The guide to hematology, under the editorship of A. I. Vorobyov and Yu. I. Loriye, page 120, M., 1979; Shapot V. S. Biochemical aspects of tumoral growth, M., 19T5; Everson T. Page of ampere-second about-1 e W. H. Spontaneous régression of cancer, Philadelphia, 1966; Foulds L. Neoplastic development, v. 1—2, L. — N. Y., 1969 — 1975; Rous P. a. To i d d J. G. Gonditional neoplasms and subthreshold neoplastic states, J. exp. Med., v. 73, p. 365, 1941.
V. S. Shapot, A. I. Vorobyov.