Page 26 - TD-4-1

Tumor Discovery Immunohistochemistry profiling of ovarian cysts

antigen 125 (CA125), Ki-67, and p53. The expression of types. Biomarkers are biological substances or structures
these biomarkers is analyzed using imaging techniques to (antigens) produced by tumors and can be measured
distinguish between benign and malignant lesions. 29,30 to detect the presence and stages of suspected tumors.
40
Various markers play significant roles in understanding
8. ICC versus traditional diagnostic methods ovarian pathology.
A standard ICC protocol entails several key steps: CA125: CA125 is encoded by the MUC16 gene.
sample preparation, fixation, permeabilization, blocking, It is one of the earliest known biomarkers of ovarian
immunolabeling, counterstaining, and microscopic pathology. In healthy women, CA125 levels are typically
imaging of stained cells. Each step requires optimization, as below 36 units/mL. 40-42 Elevated serum levels of CA125
experimental variables can significantly impact the overall can indicate the presence of ovarian masses and other
staining outcome. 31-33 Traditional diagnostic methods for pathologies, such as uterine fibroid, endometriosis,
ovarian cysts include ultrasound, computed tomography pelvic inflammatory disease, and liver cirrhosis. While
43
(CT) scans, and magnetic resonance imaging (MRI). While approximately 80% of women with advanced epithelial
these techniques provide essential cytomorphological ovarian cancer exhibit elevated levels of CA125, about
information about the cyst’s appearance and size, they are 50% of cases with early-stage ovarian cancer also showed
ineffective in distinguishing between benign and malignant increased levels of CA125. This drawback disqualifies
cysts. Studies indicate that the sensitivity and specificity CA125 as a marker for ovarian cancer screening. When
44
of these traditional diagnostic techniques range between used independently, CA125 has a sensitivity of 60% and
60% and 70%. In contrast, ICC has shown improved specificity of 90%, with higher sensitivity and specificity
34
sensitivity and specificity for differentiating benign from observed in postmenopausal women as compared to
malignant cysts. A study by Li et al. showed that a panel premenopausal women. Integrating CA125 into the risk
35
of antibodies targeting CA125, p53, and Ki-67 yielded a malignancy index algorithm (a risk assessment of ovarian
sensitivity of 93% and a specificity of 95% in distinguishing cancer in clinical settings) enhanced its sensitivity to 87%
between benign and malignant cysts. Similarly, Lee et al. and specificity to 97% for the detection of ovarian cancer.
36
45
demonstrated that ICC yielded a sensitivity of 91% and a However, CA125 is not suitable for early-stage detection
specificity of 94% for detecting malignant ovarian cysts. of ovarian cancer. It offers a good diagnostic value for
9. Advantages and limitations of ICC epithelial ovarian cancer, although its level is also elevated
in benign ovarian cysts. 45
The use of ICC in ovarian cyst profiling offers several
advantages over traditional diagnostic techniques. It is a non- Kallikreins (KLKs): KLKs are part of a 15-member
invasive, time-saving, and cost-effective technique. ICC KLK human gene family located on chromosome 19q.
37
allows for accurate antigen localization and offers improved Their diagnostic and prognostic utility in cancer has been
specificity and sensitivity in distinguishing between benign demonstrated in many studies. Twelve out of 15 members
and malignant cysts, thereby reducing the likelihood of are upregulated in ovarian cancer, and these biomarkers are
unnecessary surgical interventions. In addition, it facilitates expressed in the endocrine epithelium. They are regulated
the detection of specific biomarkers associated with benign by cancer hormones and are released and detected in
and malignant lesions, which is crucial for therapeutic various body fluids. 46,47 A study measuring the pre-
planning. It is often applied in both clinical and basic operative serum levels of human KLK10 in 318 participants
38
research. However, ICC has limitations. One of the biggest found significantly elevated results in 146 patients with
limitations of ICC is the difficulty in standardizing the ovarian cancer. The specificity and sensitivity of KLKs were
procedure due to the variations in specimen preparations, reported to be 75% and 77%, respectively. 48
unlike ICC, which uses FFPE tissue sections. This variability Osteopontin (OPN): OPN is a glycophosphoprotein
can affect the interpretation of results, leading to diagnostic expressed in ovarian cancer, as well as in cervical,
variability across different laboratories. Moreover, the gastric, endometrial, hepatocellular, prostate, and breast
choice of antibody panels in immunocytochemical profiling cancers. Its secretion is primarily attributed to activated
may differ among laboratories, contributing to diagnostic T-lymphocytes, leukocytes, and macrophages found at sites
variability. A false negative result may occur due to of inflammation and within the extracellular matrix. OPN,
inadequate samples or low cellularity. 39 first discovered in 2001 from RNA isolated from ovarian
cancer cell lines, is associated with tumor progression,
49
10. Markers in ovarian pathology invasion, and metastasis. A study showed that OPN levels
Tumor markers have emerged as critical diagnostic tools are more elevated in epithelial ovarian cancer compared
for characterizing and differentiating between tumor to ovarian cyst. Moreover, the study also revealed that
50

Volume 4 Issue 1 (2025) 18 doi: 10.36922/td.5369