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THE PROGNOSTIC VALUE OF THE EXPRESSION OF P53 IN
SQUAMOUS CELL CERVICAL CARCINOMA
Khudjamkulova G.I.
xujamkuloveldor916@gmail.com
https://doi.org/10.5281/zenodo.13888634
The actuality
of the topic is due to the high prevalence of cervical cancer,
its diagnosis mainly at latestages and unsatisfactory treatment results, which
requires improvement of screening methods and treatment of patients with
this form of the disease.
Objective:
To investigate the expression of the cancer protein p53 as a
potential prognostic marker for the effectiveness of preoperative chemotherapy,
radiation, and combined treatments on cervical cancer during patient
examination. The p53 gene is a tumor suppressor gene that functions in normal
cells through the simultaneous activity of both alleles. However, a malfunction in
the p53 gene can occur due to the loss of one allele or mutation in the other,
resulting in overexpression of the cancer protein p53 or the emergence of a
mutant form, leading to a loss of its ability to inhibit cell proliferation. This
uncontrolled proliferation can lead to tumor cell growth. There is widespread
discussion about the prognostic significance of cancer protein p53 in cervical
cancer patients. Some foreign studies have not found a clear connection between
overexpression of p53 protein (or presence of a mutation in the p53 gene) and
clinical course of disease. Others believe that the expression of the mutated
cancer protein p53 is responsible for the development of tumors with a poor
prognosis.
Materials and methods:
the biopsy and surgical material of 40 patients
(aged 25 to 70 years) with squamous cell carcinoma of the cervix of the Ib-III
stage before and after receiving combined treatment was analyzed. The size of
the cervix was compared before and after the treatment (according to the
results of ultrasound examination of the pelvic organs). The histological
structure of the tumor, the severity of therapeutic pathomorphosis and the
expression of cancer protein p53 were determined using Dako monoclonal
antibodies (clone DO-7), EnVision TM + Dual Link imaging system and DAB
chromogen (Dako). The results of the study: The cervix was enlarged in all cases
before the treatment. After the therapy, in 38 out of 40 cases, its volume and size
decreased. According to the histological structure, highly differentiated cancers
were observed in 6 cases, moderately differentiated cancers in 16, low–grade
cancer from small cells in 4 cases and squamous cell carcinoma from large cells
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in 12 cases. The degree of therapeutic pathomorphosis in 20 patients was
determined as 1-2, in 18 women – 2-3 and in 4 patients – 4. Expression of p53
before therapy was observed in 30 cases (75%). Initially, high expression (in
more than 10% of tumor cells) was detected in 22 cases (55%), weak in 8 cases
(20%), and p53 was absent in 10 cases (25%). Increased expression after
treatment was observed in 22 cases with both an initially high p53 index (14
cases) and in observations with initially weak or absent expression (8 cases).
There was a decrease in p53 in 6 cases (4 with an initially high p53, 2 with a low
ones). In 6 cases, expression was absent both before and after the therapy. In 6
cases, p53 remained unchanged (2 cases with weak expression, 4 with
pronounced expression). In 60% of cases with initially high p53 levels or its
enhancement during treatment, therapeutic pathomorphosis was low (1-2
degrees). In 33.3%, the degree of pathomorphosis was regarded as 2-3. In only
two cases (6.6%), the degree of pathomorphosis was regarded as 3-4, but at the
same time, the intensity of staining of preserved tumor cells after therapy
increased and clinically, further progression of the disease with bladder
germination and liver metastases was noted in the patient. In all cases with
initially low p53 expression, the degree of pathomorphosis was exclusively 1-2.
However, in four cases, after the therapy, an increase in the accumulation of p53
was noted (in two – pronounced, in the others– weak). In the observation with a
marked increase in expression after treatment, there was also a sharp increase
in mitotic activity (up to 25 mitoses in the field of vision). In the case of a slight
increase in p53 after therapy, despite a marked regression of the tumor (a
decrease in tumor volume by 68%), tumor emboli in the vascular lumen were
noted. In another case, multiple tumor emboli were noted, but the accumulation
of p53 after therapy was somewhat reduced.
In cases with no expression of cancer protein p53 before treatment, the degree
of pathomorphosis was assessed as 1-2 (4 cases) and 2-3 (6 cases). After the
therapy, in two cases with the initial absence of p53, very weak expression of the
marker appeared. Clinically, in 4 cases, the disease progressed with continued
growth in the pelvis. Thus, these cases do not fit into the general idea of the
relationship between p53 expression and disease prognosis.
Conclusions:
The degree of differentiation of squamous cell carcinoma did not
correlate either with the level of expression of cancer protein p53 or with the
degree of therapeutic pathomorphosis. The expression of p53 of varying severity
in the primary material was observed in 75% of cases. Despite the decrease in
the size of the cervix during treatment, a low degree of therapeutic
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pathomorphosis was observed in 60% of cases. An increase in the expression
level of cancer protein p53, which was accompanied by a low degree of
therapeutic pathomorphosis, was noted in 55% of women, and in some cases
this was accompanied by a sharp increase in mitotic activity, continued tumor
growth, and distant metastasis within 1-2 years after surgery. This pattern was
accompanied by a low degree of therapeutic pathomorphosis. In the case of a
high degree of pathomorphosis, tumor cells with high expression of cancer
protein were preserved. Thus, the expression level of cancer protein p53 may be
significant for evaluating the effectiveness of treatment of patients at the
preoperative stage.
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