Abril - 2017

ytopathologic

evaluation

patients

submitted

radiotherapy

for

uterine

cervix

cancer

ssoc

ras

2017; 63(4):379-385

381

diolysis. After ionization, the water molecules undergo

an electronic rearrangement with the possibility of pro-

ducing free radicals due to the presence of atoms whose

last layer does not have the number of electrons that would

give stability to the structure.

15-18

DNA is a macromolecule responsible for encoding

the molecular structure of all cellular enzymes, and it is

key to the process of establishing biological damage. By

undergoing direct (ionizing) or indirect (through free

radical attack) radiation action, DNA is exposed to basi-

cally two types of damage: gene mutation and lysis.

16-19

DNA lesions are the most biologically important

because they can compromise vital processes such as cell

replication and transcription.

The different lesions pro-

duced by radiation, if left unrepaired, can compromise

important biological functions such as DNA transcription

and replication, leading to cell death. Failure to repair

damage leads to mutagenesis when they are present in

the DNA during replication.

The distribution and repair of lesions caused in DNA

depend on the nucleotide sequence, whether or not they

are in transcribed regions, and the accessibility to DNA by

its association with chromosomal proteins.

Despite the

ability of human cells to remove nucleotides damaged by

radiation by means of excision mechanisms, some lesions

remain in the genome. Radiation-induced carcinogenesis

involves the inactivation of one or more tumor suppressor

genes or the activation of pro-oncogenes. The disease can

also result from a gene product altered by a mutation.

adiotherapy

Radiotherapy is a method capable of destroying tumor

cells by employing a beam of ionizing radiation. A pre-

calculated dose of radiation is applied at a given time to

a volume of tissue encompassing the tumor, seeking to

eradicate all tumor cells with the least possible damage

to the surrounding normal cells, which play a vital role

in the regeneration of the irradiated area. Ionizing radia-

tion is electromagnetic or corpuscular in nature and car-

ries energy. By interacting with the tissues, they produce

fast electrons that ionize the medium and create chemical

effects such as water hydrolysis and the breakdown of

DNA strands. Cell death can then occur through a variety

of mechanisms, from the inactivation of systems that are

vital for the cell to its inability to reproduce. Tissue re-

sponse to radiation depends on many factors, such as

tumor sensitivity to radiation, location and oxygenation,

as well as the quality and amount of radiation, and the

total time it is administered. In order for the biological

effect to reach a greater number of neoplastic cells and

tolerance of normal tissues to be respected, the total dose

of radiation administered is usually fractionated in equal

daily doses when external therapy is used.

3,23

The rate of tumor regression represents the degree of

sensitivity of the tumor to radiation. It depends funda-

mentally on its cellular origin, its degree of differentiation,

oxygenation and the clinical presentation. Most radio-

sensitive tumors are radiocurable. However, some tumors

spread despite local control and others have their sensitiv-

ity so close to that of normal tissues that it is not possible

to apply the eradication dose. Local curability is only

achieved when the dose of radiation applied is lethal to

all tumor cells, but does not exceed the tolerance of nor-

mal tissues.

3,23

Radiotherapy is used in approximately 60% of all di-

agnosed cases of malignant tumors, including those most

prevalent in Brazil, namely prostate, lung, breast and cer-

vical cancers. This means that, out of every 100 patients,

60 will undergo radiotherapy in one of their evolutionary

stages.

19,23

In recent times, the most significant develop-

ment in the treatment of locally advanced cervical carci-

noma has been the introduction of radiochemotherapy.

However, there are some impediments to its administration,

including elderly patients, patients with pre-existing dis-

eases and patients who refuse chemotherapy. There are

also financial issues, such as the cost of chemotherapy and

the cost of managing toxicities.

ervical

cancer

Squamous or epidermoid carcinoma accounts for more

than 80% of malignant cervical neoplasms. Adenocarci-

noma (endocervical adenocarcinoma, endometrioid, clear

cells, adenocystic, adenosquamous) is a less frequent

type that affects the glandular epithelium and corre-

sponds to about 10% of the cases.

1,8

Other histopatho-

logical types that appear less frequently are sarcomas

(embryonal rhabdomyosarcoma [children] and leiomyo-

sarcoma), melanoma, small cell carcinoma (neuroendo-

crine), and metastatic carcinoma.

8,24

The main risk factor for the development of cervical

cancer is persistent infection with human papillomavirus

(HPV) associated with cofactors, especially immunosup-

pression and smoking. The mean age of women with this

diagnosis is 51.4 years. Squamous carcinoma progresses

from precursor stages, the so-called intraepithelial lesions.

Low-grade lesions may progress over time to high-grade

lesions. Then, neoplastic cells can rupture the basement

membrane and invade the underlying stroma. However,

some tumors do not appear to start as low-grade lesions,

evolving from high-grade lesions from the beginning.

7,25