European International Journal of Multidisciplinary Research
and Management Studies
33
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TYPE
Original Research
PAGE NO.
33-36
DOI
OPEN ACCESS
SUBMITED
27 April 2025
ACCEPTED
23 May 2025
PUBLISHED
25 June 2025
VOLUME
Vol.05 Issue06 2025
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Diagnostic Value of VEGF
And Ki-67 Expression in
Predicting Recurrence Risk
in Ovarian Cancer
Nigora Zaripovna Babajanova
Oncogynecologist, Radiotherapist, Republic Specialized Scientific-Practical
Medical Center of Oncology and Radiology, Tashkent Regional Branch,
Tashkent, Uzbekistan
Yashnar Salievna Mamadaliyeva
Oncogynecologist, Center for Professional Development of Medical
Workers, Tashkent, Uzbekistan
Abstract:
This article assesses the clinical and prognostic
value of VEGF and Ki-67 immunohistochemical markers
in patients diagnosed with ovarian cancer. A total of 130
patients treated at the Tashkent Regional Branch of the
Republican Oncology and Radiology Center between
2018 and 2022 were included in the study. Expression of
the markers was evaluated using H-score and
percentage index methods. Results demonstrated that
high levels of VEGF and Ki-67 expression were
significantly associated with increased recurrence risk
(p<0.001). Kaplan
–
Meier survival analysis and Cox
regression confirmed the independent prognostic
significance of these markers. The potential for
developing an immunohistochemical prognostic panel
to guide individualized therapeutic strategies and
determine the necessity of adjuvant therapy is
discussed.
Keywords:
Ovarian cancer, VEGF, Ki-67, recurrence,
immunohistochemistry, prognosis, biomarkers.
Introduction:
One of the most pressing challenges in
oncogynecology is ovarian cancer (OC). It remains a
leading cause of cancer-related death among women
and is frequently diagnosed at an advanced stage,
characterized by high recurrence rates. Even with
radical surgery and combined treatment, recurrence
occurs in a significant proportion of patients.
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and Management Studies
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European International Journal of Multidisciplinary Research and Management Studies
Studies indicate that nearly 60% of recurrences occur
within the first 18
–
24 months, pointing to the
aggressive nature of the disease and resistance to
standard treatment protocols. In this context,
identifying recurrence risk in advance, evaluating
patient prognosis, and developing individualized
treatment plans are critical tasks.
In recent years, biological markers have expanded the
possibilities for assessing tumor behavior and
predicting recurrence. Immunohistochemical markers
such as Ki-67 (proliferation index) and VEGF
(angiogenesis marker) are recognized as important
indicators of tumor growth, dissemination, and
therapy responsiveness.
VEGF and the Role of Angiogenesis
: VEGF (Vascular
Endothelial Growth Factor) is one of the key factors
that promote the formation of blood vessels in tumor
tissues. It plays a central role in enhancing tumor
invasiveness and metastatic potential. Synthesized
intensively by tumor cells, VEGF stimulates the growth
of blood capillaries, which improves oxygen and
nutrient supply to the tumor and facilitates its rapid
expansion. Research shows that patients with high
VEGF expression levels have significantly increased
recurrence risk and decreased survival rates.
Ki-67 and Cell Proliferation
: Ki-67 is a nuclear antigen
and a marker of cell proliferation. It is detected only in
mitotically active cells and is used to evaluate the
tumor's growth rate. In ovarian cancer, high Ki-67
expression indicates aggressive tumor behavior,
increased biological activity, and reduced sensitivity to
treatment. Consequently, such patients often
experience rapid and severe recurrence.
Scientific
and
Practical
Relevance
:
Studies
demonstrate that combined evaluation of VEGF and Ki-
67 provides a more comprehensive picture of tumor
proliferative and angiogenic properties. This supports
individualized prognosis, identification of high-risk
groups, selection of intensive therapeutic strategies,
and improved treatment effectiveness. Particularly, it
aids in evaluating the necessity of adjuvant
chemotherapy, helping to avoid both overtreatment
and undertreatment.
Despite the high rate of late-stage diagnoses,
chemoresistance, and recurrence in ovarian cancer in
Uzbekistan, systematic clinical evaluation of VEGF and
Ki-67 is not yet fully established. This study has
scientific and practical significance for advancing local
oncological practice.
Objective
: To assess VEGF and Ki-67 expression levels
in ovarian cancer patients, analyze their correlation
with recurrence risk, and determine their clinical-
diagnostic value.
Literature Review
Ovarian cancer is associated with high mortality and
late-stage detection. Recurrence significantly reduces
survival. Thus, identifying reliable biomarkers for early
prediction of recurrence is essential. In recent years,
VEGF
and
Ki-67
have
emerged
as
major
immunohistochemical markers studied for their
prognostic utility.
VEGF is a central regulator of angiogenesis in tumor
tissues. Under normal conditions, it is expressed in
response to hypoxia, but in tumors, its hyperexpression
promotes growth and metastasis. Folkman (1971) was
the first to establish that angiogenesis is essential for
tumor progression. Accordingly, high VEGF expression is
logically associated with higher recurrence risk.
Sugiyama et al. (2010) demonstrated that VEGF
expression in 87 patients with serous carcinoma
negatively correlated with recurrence-free survival.
Similarly, Linderholm (2009) showed that high VEGF
expression was associated with <30% 5-year survival.
Kikuchi et al. (2018) linked VEGF expression with
platinum resistance, suggesting its use in predicting
treatment response. Moreover, VEGF is a biological
target for anti-angiogenic therapy (e.g., bevacizumab).
Ki-67, located in the cell nucleus and expressed during
mitosis, is a widely studied marker of proliferative
activity. Using MIB-1 antibodies, tumors with Ki-67
index >20% are classified as aggressive. Loizzi et al.
(2013) found that patients with Ki-67 >40% had 2.5
times higher recurrence rates.
A meta-analysis by Morice et al. (2012) found that
patients with high Ki-67 expression had a 1.7 times
higher recurrence risk and significantly lower overall
survival. Mahdi et al. (2014) reported that even in early-
stage OC, high Ki-67 expression predicted recurrence.
METHODS
This retrospective-prospective cohort study was
conducted at the Tashkent Regional Branch of the
Republican Oncology and Radiology Center from 2018
to
2022.
Clinical,
morphological,
and
immunohistochemical data were comprehensively
analyzed.
Inclusion Criteria:
•
Age: 30
–
80 years
•
Histologically confirmed ovarian cancer
(epithelial and non-epithelial types)
•
FIGO stages I
–
III
•
Available biopsy materials and paraffin-
embedded tissue blocks
Tumor tissues were fixed, embedded in paraffin, and
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European International Journal of Multidisciplinary Research and Management Studies
stained with H&E. Tumors were categorized as serous
adenocarcinoma, mucinous tumors, endometrioid
carcinoma, clear cell tumors, Brenner tumors, and
mixed types.
Immunohistochemistry (IHC):
IHC analysis was conducted using monoclonal
antibodies specific for VEGF and Ki-67 (DAKO, Thermo
Fisher). Slides were cut to 3
–
5 µm and stained on the
Ventana BenchMark XT system.
Ki-67 Scoring: 0
–
10%: low proliferation. 11
–
25%:
moderate. 25%: high proliferation
VEGF Scoring: 0: no expression. 1: weak. 2: moderate
3: strong expression
H-score Calculation: H-
score = Σ (intensity × % of
positive cells)
Recurrence Evaluation Criteria: Clinical-laboratory
confirmation.
Radiological
(CT/MRI)
evidence.
Symptomatic or ascitic recurrence
Statistical Analysis: Data were analyzed using
Microsoft Excel 2021 and SPSS v26.. Comparative tests:
Chi-
square, Fisher’s exact test. Survival analysis:
Kaplan
–
Meier.
Multivariate
regression:
Cox
proportional hazards model. Correlations: Spearman
and Pearson coefficients
Significance threshold: p < 0.05
Ethics: Study approved by the Tashkent Oncology
Center Ethics Committee (Order №03
-02, 2023).
Written informed consent was obtained from all
patients.
RESULTS
Among 130 ovarian cancer patients, three groups were
analyzed: epithelial tumors (65), non-epithelial tumors
(35), and a control group without recurrence (30).
1. VEGF Expression: High VEGF (+++) was present in
62.1% of recurrence cases vs. 13.3% of non-recurrence
(p<0.001). Odds Ratio = 5.2 (CI: 2.3
–
11.8)
2. Ki-67 Index: Patients with Ki-67 >40% had a
recurrence rate of 51.5%, compared to 10.0% in those
with <20%. HR = 4.9 (CI: 2.1
–
10.2)
3. Correlation Between VEGF and Ki-67: Spearman r =
0.46
(p<0.01),
indicating
moderate
positive
correlation.
4. Kaplan
–
Meier Survival Analysis: VEGF+++, Ki-
67>40%: median RFS = 14.5 months VEGF+, Ki-67<20%:
median RFS = 32.6 months
Log-rank p < 0.001
5. Cox Regression (Multivariate): VEGF+++: HR = 2.87
(CI: 1.46
–
5.63, p=0.002). Ki-67 > 40%: HR = 3.12 (CI:
1.58
–
6.09, p=0.001). FIGO Stage III: HR = 2.34 (CI: 1.12
–
4.93, p=0.028)
DISCUSSION
This study confirms that VEGF and Ki-67 are reliable
markers for predicting recurrence risk in ovarian cancer.
High VEGF indicates enhanced angiogenesis and
potential for metastasis, while high Ki-67 reflects mitotic
activity and tumor aggressiveness. Their combined
evaluation provides a robust prognostic platform.
International
studies
(Linderholm,
Yamamoto,
Sugiyama) support our findings. Bevacizumab, an anti-
VEGF agent, is recommended in high-VEGF cases. High
Ki-67 suggests the need for tailored adjuvant therapy.
CONCLUSION
VEGF
and
Ki-67
are
highly
reliable
immunohistochemical
markers
for
predicting
recurrence in ovarian cancer. Combined use enhances
individualized treatment planning. Kaplan
–
Meier and
Cox analyses confirm their independent prognostic
value. Recommended for integration into standard
diagnostic protocols. Further studies should expand
sample size and include additional molecular markers
(e.g., HER2, p53, CD34).
Practical Recommendations
: Include VEGF and Ki-67 in
routine IHC panels for ovarian cancer. Use marker levels
to stratify recurrence risk and guide adjuvant therapy.
Develop and validate a prognostic index combining
VEGF/Ki-67 with clinical staging.
Final Remark
: The combined expression of VEGF and Ki-
67 offers a modern, reliable, and individualized
approach to prognosis in ovarian cancer.
REFERENCES
Prat J. A synopsis of the 2014 WHO classification of
tumors of the female reproductive organs. Mod Pathol.
2015.
Bell D. et al. Integrated genomic analyses of ovarian
carcinoma. Nature. 2011.
McCluggage WG. Morphological subtypes of ovarian
carcinoma. Histopathology. 2011.
Kurman RJ, Shih IM. The origin and pathogenesis of
epithelial ovarian cancer. Am J Surg Pathol. 2010.
Köbel M. et al. Differences in tumor biology between
histological subtypes of ovarian cancer. Int J Gynecol
Pathol. 2014.
Yemelyanova A. et al. Immunohistochemical p53
staining in ovarian cancer. Mod Pathol. 2011.
Cannistra SA. Cancer of the ovary. N Engl J Med. 2004.
Ferrara N. VEGF: basic science and clinical progress.
Endocr Rev. 2004.
Hlatky L, Hahnfeldt P. Clinical implications of
angiogenesis in cancer. N Engl J Med. 1996.
American Cancer Society. Ovarian Cancer Statistics.
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and Management Studies
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European International Journal of Multidisciplinary Research and Management Studies
2023.
