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Tumor Discovery                                                 Immunohistochemistry profiling of ovarian cysts



              AXL receptor: AXL receptor is a member of the tyrosine   for definitive diagnosis. AI and ML offer the advantage
            kinases family of receptors, known to promote cell survival   of reducing false-positive and false-negative results.
            and inhibit apoptosis, thereby playing a significant role in   Integrating ICC with molecular diagnostics and AI could
            ovarian cancer progression. AXL is often overexpressed   enhance diagnostic precision.  Further studies have
                                                                                         88
            in ovarian cancer cells, making it a biomarker of interest.   explored the combination of the ICC method with other
            Its positive regulation is associated with tumor metastasis,   diagnostic techniques such as CT, ultrasound, and MRI.
                                                                                             89
            aggressiveness, and resistance to conventional therapies.   A conducted by van den Brule et al.  revealed that the
            Activation of AXL signaling pathways can lead to epithelial-  combination of ICC and ultrasound yielded a sensitivity
            to-mesenchymal transition, facilitating cancer cell   of 98% and specificity of 96% in diagnosing malignant
            invasion. In addition, AXL can evade antitumor immune   ovarian cysts. Similarly, Lee  et al.  discovered that the
                                                                                           36
            response, contributing to its role in cancer progression. 80,81  combination of ICC and MRI yielded a sensitivity of
              CA72-4: CA72-4 is a tumor-related glycoprotein and   97% and specificity of 95% in the diagnosis of malignant
            a specific epitope on MUC1. An unusual increment of   ovarian cysts.
            CA72-4 has been reported in ovarian cancer, although the   Future directions focus on multiplex ICC for
            levels are not affected by menstrual cycle, pregnancy, and   simultaneous detection of multiple markers and digital
            endometriosis, but are slightly affected by inflammatory   pathology for  enhanced  accurate  results  and consistent
            conditions. This stability suggests that CA720-4 could   interpretations, 90,91   Novel biomarkers, such as YKL-40
            serve as a potential diagnostic marker for ovarian cancer.   and mesothelin, are being investigated for their potential
            Moreover, a study detected overexpression of CA72-4 in   to  improve  ovarian  cancer  diagnosis  and  prognosis.
            mucinous tumors and clear ovarian cell carcinomas, while   Researchers are also working towards improving the
            CA125 and HE4 levels were not elevated in those two   standardization of ICC practice and existing techniques. 92,93
            histotypes. 82                                     12. Conclusion
              The 21  century is witnessing emerging ICC biomarkers
                    st
            for ovarian cysts. They include Ki-67, p53, and WT1.    ICC has emerged as a critical diagnostic tool for
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            Studies have shown that ICC biomarkers, such as CA-125   distinguishing  between  benign  and  malignant  ovarian
            and Ki-67, are frequently used to detect benign ovarian   lesions. The use of a panel of antibodies targeting specific
            lesions. CA-125 is said to be elevated in benign ovarian   biomarkers  (antigens)  associated  with  benign  and
            cysts such as endometriosis and cystadenomas. Ki-67 is   malignant ovarian cysts provides a high level of sensitivity
            associated with cellular proliferation.  Benign cystic lesions   and specificity compared to traditional diagnostic
                                         84
            typically show low expression of malignant biomarkers.    techniques. ICC significantly enhances the diagnostic
                                                         85
            Malignant ovarian lesions often express p53, HE4, and   accuracy of ovarian cysts, providing a distinction between
            WT1. p53 mutations are particularly associated with high-  benign from malignant lesions with greater precision than
            grade serous carcinomas, while HE4 and WTI are specific   traditional methods. Key biomarkers such as CA-125, HE4,
                                86
            to ovarian malignancies.  A study has demonstrated that   p53, and Ki-67 play critical roles in this distinction. Despite
            a combination of CA-125 and HE4 enhanced diagnostic   its strength, ICC poses several limitations. However,
            accuracy for ovarian cancer. 87                    the combination of ICC with other advanced diagnostic
                                                               methods holds the potential to enhance the diagnosis and
            11. Current state of research and future           management of ovarian cysts, leading to improvement in
            directions                                         patient outcomes. Ongoing research is aimed at improving
                                                               protocol  standardization,  discovering  novel  markers,
            The  application of ICC in ovarian cyst diagnosis is a   exploring multiplex marker panels, and integrating ICC
            rapidly evolving method, with ongoing research aimed at   with other diagnostic methods.
            improving diagnostic accuracy and consistency. A critical
            area of concern is the development of standardized   Acknowledgments
            antibody panels for use across laboratories. Artificial   None.
            intelligence (AI) and machine learning (ML) algorithms
            are emerging fields of research that aim to improve   Funding
            the interpretation of results and enhance objectivity
            and consistency. AI algorithms can analyze complex   None.
            signaling and imaging data, enabling early detection and   Conflict of interest
            characterization of ovarian cysts, by recognizing unique
            patterns and identifying easily missed features, allowing   The authors declare that they have no competing interests.


            Volume 4 Issue 1 (2025)                         21                                doi: 10.36922/td.5369
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