Tumors result from carcinogenesis and loss of control
of normal cells. The major biological characteristics of cancer
cells include abnormal appearance, functions, metabolism and uncontrollable
proliferation. Uncontrollable growth is the major reason responsible
for so many tumor-specific manifestations on morphology and pathology.
A series of clinical symptoms, such as pain, loss of weight and
even death occur due to a large amount of cells pile up and result
in mass rapidly, as well as the fast-growing tumor cells transferring
to other regions of human bodies.
1. Mechanism of carcinogenesis
There are many reasons that can result in tumor cells, which include
a variety of carcinogenic factors, such as chemicals, radiation,
viruses and etc. It is also related to the abnormality of DNA, inheritance
as well as the immune and endocrine systems. Although almost everybody
might have contacted carcinogenic factors, not everyone can develop
cancers. The susceptibility is largely related to individual inherited
condition. The abnormal growth and differentiation of malignant
cells is because they have escaped from the normal cell controlling
mechanism. And the uncontrollable growth is due to the defect of
the genes controlling cell division, for example, the abnormality
of genes in leukocytes can result in leukemia. Therefore, tumors
can be called as a kind of genetic deficiency. Changes in genetic
material can easily occur at active cell proliferation stages, such
as pregnancy, infancy and early childhood. At these stages, many
organs and systems can grow and differentiate rapidly and numerous
cell divisions occur. Therefore the possibility of normal cells
transforming into malignant cells resulted from one or more genes
mutations are correspondingly increased.
A
tumor is a kind of disease caused by many reasons, via multiple
stages and multiple mutations. Almost all of tumors are originated
from a single mutated cell. Before they show clinical manifestations,
these cells usually have existed for more than ten years. During
this period, carcinogenic cells usually experienced four times but
less than ten times of mutations (Figure 1). The first mutation
makes the mutated cell easier to divide than normal cells. This
mutated cell and its offspring become very active, which is called
hyperplasia. At a certain point of this stage, one of these cells
undergoes mutation again, which makes the division of its offspring
uncontrollable and show an abnormal appearance, which is usually
called abnormal growth. Following that, a cell undergoes another
mutagenesis. The growth and appearance of this cell and its offspring
show to be abnormal. If the mutated cells still stay at the original
location, it is called original cancer. However, if some of the
cells undergo another mutation, which makes it possess the ability
to invade other organs, the tumor has been changed into malignancy.
Therefore, cancergenisis is the result of accumulation of mutations.
These mutations enable malignant cells to grow rapidly and/or to
block apoptosis, or to possess both features. At present, the study
of molecular biology show that the abnormality of two groups of
genes (oncogenes, tumor-suppressor genes) play significant roles
in the occurrence of tumors. When oncogenes are activated and/or
tumor-suppressor genes are lost, cancers may occur. Under normal
conditions, cancer genes play regulatory effects on the growth,
differentiation and development of cells. However, during the processes
of chromosome translocation, point mutations and gene duplications,
cancer gene could be activated abnormally, which results in abnormal
cell growth. But the loss of tumor-suppressor genes is achieved
by a way that many mutations appear in cells, loss, rearrangements
and point mutations. All these changes can result in loss of cell
growth inhibition, which can further cause cancers.
2. Characteristics of tumor growth
The characteristics of tumor growth include growth speed and growth
pattern. In comparison to normal cells, the growth of tumor cells
is much faster. Generally speaking, well-differentiated benign tumors
grow relatively slow but low-differentiated malignant cells grow
faster. Clinically, the double time of tumor is about 20-120 days.
However, if a tumor is originated from a cell, it will take about
30 duplication times until a 1 cm tumor mass containing 1 billion
cells is formed. In terms of growth pattern, tumor growth includes
expansive, infiltrative and exogenous growth. Expansive growth is
the major growth pattern of most malignant tumors. As tumor size
increase, it can expand and compress the surrounding tissues but
do not invade tissues nearby. The major clinical manifestations
of this type of tumors include pressing and blocking symptoms. Infiltrative
growth is the major growth pattern of malignant tumors (Figure 2A).
Due to loss of contact inhibition, malignant cells will have the
ability of invasion and metastasis. Tumors extend to the adjacent
tissues in a way similar to roots infiltrating into the adjacent
tissue space, blood vessels, lymphatic ducts and etc, which makes
them difficult to be separated from the adjacent tissues. Therefore,
they are not easy to be removed by operation and may be easier to
relapse after operation.
3. Tumor morphology and structural characteristics of the tissue
The number of tumors could be a single mass, but could be also appear
in diverse tissue types as multiple tumors. From the appearance,
the tumors present with a variety of forms, including nodular, lobular,
cauliflower-like, papillary, cystic and ulcerative shapes (Figure
2B). Tumors growing on skin and mucosa usually are shown to be nodular,
lobular and cauliflower-like. In addition, the size of tumors is
not consistent, from invisible by eye to as large as forty kilograms,
such as ovarian cystadenoma. Based on appearance, tumor exhibits
offwhite color, but the color is also different based on the amount
of blood in the tumors. The hardness of tumors is determinated by
the nature of in the parenchyma and the amount of the fiber in stroma,
for example, fatty tumors is the softest one but osteoma is very
hard.

Tissue composition of tumors is very diverse. But these tissues
can basically divided into parenchyma and stroma. Parenchyma refers
to cancer cells, which determines the characteristic of tumors.
Stroma is mainly composed of blood vessels and fiber tissues, which
is mainly for providing parenchyma with nutrition and support. Generally,
benign tumor are very similar to their originated tissues, therefore
their origin can be identified by the tumor structures. For example,
fibroma is very similar to normal fiber tissue with only difference
on pattern of arrangement from normal tissues, exhibiting network
pattern. Malignant tumors are however quite different from their
originated tissues. Their cells distribute chaotically and loss
of normal pattern and organization. For example, fibrosarcoma have
more tumor cells, less fibers, disordered arrangement, which is
quite different from normal fibrous tissues.
4. Morphological characteristics of tumor cells
The difference between tumor cells and normal cells is that the
differentiation of the former is relatively lower, which can't reach
to normal maturation. Benign tumors cells have relatively high differentiation,
which is similar to their originated tissues; but malignant tumor
cells have low level of differentiation. They are quite different
from normal cells on morphology, functions and metabolism and exhibit
irregular size and shape. Another prominent changes include changes
of cell nucleus and skeleton. They are important in the determination
of the clinical characteristics of tumors.
Nucleus: The shape and structure of cell nucleus are quite
different from those of normal originated tissues. The nucleuses
enlarge and the shape becomes irregular. Due to the increase of
DNA, the number of chromosomes also increases correspondingly. Therefore,
they appear to be crassitude, dark staining and irregularly distributed.
Meanwhile, due to the increased demand of protein synthesis, the
amount of rRNA in nucleolus also increases, nucleolus also enlarges
and the numbers also increase. In addition, it usually exhibits
pathological caryokinesis, such as asymmetry and multipolarity etc
(Figure 3). All these changes become important indicator of tumor
diagnosis, grading and staging.

Cell skeleton: Under electron microscope, it was found that
the distribution and activity of cellular microtubules and microfilaments
have undergone great changes. These changes in turn result in changes
of cellular morphology, the relationship between the adjacent cells
as well as the adherence and mobility. Due to the decrease of the
adherence between tumor cells and cell-cell matrix, the decrease
of adherence makes cells capable of moving, migration and spreading.
This is one of the reasons of tumor shedding, infiltration and metastasis.
Other changes: Other cellular organelles such as mitochondria,
endoplasmic reticulum and Golgi apparatus etc are usually not rich,
irregular, strange-shaped and irregularly distributed. In addition,
tumors can also generate some enzymes, which can digest the adjacent
barrier nearby and therefore make them capable to invade tissues
nearby.
5. Metabolic characteristics of tumor cells: Because tumor
cells grow very rapid, their metabolism is also very active too.
Although tumor cells are similar to normal cells in nature, there
is prominent difference in terms of quantity. For example, tumor
cells mainly use glycolysis to obtain energy, which is mainly caused
by functional deficiency in mitochondria. In addition, as described
before, the synthesis of DNA and RNA also increase in tumor cells.
The increase of these inherited materials is related to the division
of tumor cells and proliferation. The changes of the enzymes in
tumor cells are also very complicated. Some of them are increases
and some of them decreased. For example, oxidases (cytochrome oxidase
and succinic dehydrogenase) decrease, but the acid phosphatase increase
dramatically in prostate cancer. In addition, protein metabolism
is also increased in order to meet the need of cell growth.
6. Tumor markers: Tumor markers are the synthesized products
of tumor cells or generated by human body in responsive to tumors.
Some of these proteins are tumor-type specific and some are also
expressed in other tumors. Some of the tumor-type specific markers
include tumor specific antigens, tumor specific enzymes and tumor
specific hormones. These markers are very important in making early
diagnosis, appraisal of clinical efficacy and prognosis. The markers
used for screening could be highly specific for tumor patients who
are at early stages, asymptomatic and curable. For example, PSA
can be used in screening prostate cancers. CEA can be used in prognosis
and examination of residual tumors to test the degree of malignancy.
The increase of CEA level suggests that tumor relapse and prognosis
are bad. At present, only a limited number of markers have been
clarified. Researches on these markers are significant to tumor
diagnosis and prevention.
7. Other tumor characteristics: Except for the characteristics
mentioned above, other fields that are being studied extensively
include tumor related genes (oncogenes, tumor-suppressor genes and
susceptibility genes); apoptosis and cell differentiation; cell
cycle and signal transudation; gene engineering and gene engineered
antibody; cytokines; tumor drug resistance and reversion; tumor
metastasis and reversion, tumor immunology, etc. Elucidation of
these mechanisms will generate deeper influence to prevention and
treatment of tumors.
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