Histopathological and Immunohistochemical Expression of Ki-67 and Alpha-Fetoprotein as Indicators in Various Gallbladder Diseases
DOI:
https://doi.org/10.52783/jns.v14.3682Keywords:
Ki-67, alpha-fetoprotein, gallbladder, cholecystitis, IHCAbstract
Background: Gallbladder disease encompasses a spectrum of conditions affecting the gallbladder, including cholelithiasis (gallstones), cholecystitis (inflammation), gallbladder polyps, and gallbladder cancer. These disorders are influenced by multiple factors such as genetic predisposition, metabolic dysfunction, inflammatory pathways, and biliary stasis. Aim: This study aimed to evaluate the histopathological and immunohistochemical expression of Ki-67 and alpha-fetoprotein (AFP) in gallbladder tissue.
Methods: This study was conducted at the College of Science, Wasit University, Iraq. Samples were collected from the Al Karama Teaching Hospital and Al Zahraa Hospital between October 2023 and July 2024. The study included 40 patients with cholecystitis (9 males and 31 females, aged 20–80 years) and 10 normal samples. The pathological classification categorized samples into acute cholecystitis, chronic cholecystitis, and hyperplasia. Immunohistochemical analysis was performed to assess in situ the Ki-67 and AFP expression.
Results: Ki-67 expression increased progressively across the type disease recorded 1.2% in controls, 5.7% in acute cholecystitis, 8.93% in chronic cholecystitis, and 13.9% in hyperplasia, with a statistically significant association (p< 0.001). Overall, 72.5% of the samples tested positive for Ki-67 expression. In contrast, AFP expression remained low (1.0% in controls and acute cholecystitis, 2.05% in chronic cholecystitis, and 3.73% in hyperplasia) and showed no significant association with the disease type (p> 0.05). Only 15.0% of the samples tested positive for AFP.
Conclusion: These findings indicate Ki-67 expression is significantly associated with gallbladder disease and serves as a strong marker of histopathologic lesion progression, while AFP expression remains minimal and statistically insignificant.
Downloads
Metrics
References
Al-Saltany, R. A. A. (2017). Immunogenetic study on patients with gallbladder infection in Hilla City (Master’s thesis, University of Babylon). University of Babylon.
Baba, H., Wakabayashi, M., Oba, A., Tsubomoto, T., Nakamura, H., Sanada, T., Kuwabara, H., Nakajima, K., & Goseki, N. (2014). Primary papillary hyperplasia of the gallbladder mimicking gallbladder cancer. International surgery, 99(3), 247–251. https://doi.org/10.9738/INTSURG-D-13-00252.1
Bano, S., Bakhsh, L., Wagan, G., Zardari, A. A., Bangulzai, M. A., & Shaikh, R. (2020). Study on morphological changes in the gall bladder mucosa associated with cholelithiasis. The Professional Medical Journal, 27(08), 1753-1762.
Behar, J. (2013). Physiology and Pathophysiology of the Biliary Tract: The Gallbladder and Sphincter of Oddi—A Review. ISRN Physiology, 2013, 1–15. https://doi.org/10.1155/2013/837630
Bilgin, M., Balci, N. C., Shaikh, F., Semelka, R. C., Bilgin, S. S., & Erdogan, A. (2009). Magnetic Resonance Imaging of Gallbladder and Biliary System. Topics in Magnetic Resonance Imaging, 20(1), 31–42. https://doi.org/10.1097/rmr.0b013e3181b48aa2
Brown, J. A., & Roberts, C. S. (1992). Elevated serum alpha‐fetoprotein levels in primary gallbladder carcinoma without hepatic involvement. Cancer, 70(7), 1838-1840.
Casper, M., & Lammert, F. (2011). Gallstone disease: basic mechanisms, diagnosis and therapy. Praxis, 100(23), 1403-1412
Dixit, N., Trivedi, S., & Bansal, V. K. (2021). Clear-cell adenocarcinoma of the gallbladder with alpha-fetoprotein production: a case report and review of the literature. Gastrointestinal Tumors, 8(2), 52-57.
Doval, D. C., Azam, S., Sinha, R., Batra, U., & Mehta, A. (2014). Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma. Journal of carcinogenesis, 13.
Hibino, S., Kawazoe, T., Kasahara, H., Itoh, S., Ishimoto, T., Sakata-Yanagimoto, M., & Taniguchi, K. (2021). Inflammation-Induced Tumorigenesis and Metastasis. International journal of molecular sciences, 22(11), 5421. https://doi.org/10.3390/ijms22115421
Kaur, A., Dubey, V. K., & Mehta, K. S. (2012). Gallbladder mucosal changes associated with chronic cholecystitis and their relationship with carcinoma gallbladder. JK science, 14(2), 89.
Kumar, R., Yadav, S. K., Singh, G., Gupta, R., & Singh, S. (2021). Study of expression of p53 and Ki-67 in Benign, premalignant, and malignant lesions of the gallbladder. Journal of Cancer Research and Practice, 8(3), 87-92.
Lazcano-Ponce, E. C., Miquel, J. F., Muñoz, N., Herrero, R., Ferrecio, C., Wistuba, I. I., Alonso de Ruiz, P., Aristi Urista, G., & Nervi, F. (2001). Epidemiology and molecular pathology of gallbladder cancer. CA: a cancer journal for clinicians, 51(6), 349–364. https://doi.org/10.3322/canjclin.51.6.349
Lee, J. H., Lee, K. G., Paik, S. S., Park, H. K., & Lee, K. S. (2011). Hepatoid adenocarcinoma of the gallbladder with production of alpha-fetoprotein. Journal of the Korean Surgical Society, 80(6), 440–444.
Littman, E. R., Singh, C., & Neychev, V. (2023). Gallbladder Cancer or Diffuse Xanthogranulomatous Cholecystitis: A Case of Management Dilemma During Elective Cholecystectomy With Unexpected Severe Mass-Like Pericholecystic Fibrosis and Inflammation. Cureus, 15(8).
Liu, Y., Zhu, X., Wu, Q., Zhong, Q., Chen, Y., & Zhang, Y. (2022). A functionalized magnetic nanoparticle regulated CRISPR-Cas12a sensor for the ultrasensitive detection of alpha-fetoprotein. The Analyst, 147(14), 3186–3192. https://doi.org/10.1039/d2an00697a
Mita, J., Tada, K., Kuboyama, Y., Iwaki, K., Nakamura, S., & Fukuzawa, K. (2022). Poorly differentiated adenocarcinoma with signet ring cells of the gallbladder producing a high level of alpha-fetoprotein: A case report. International journal of surgery case reports, 101, 107780. https://doi.org/10.1016/j.ijscr.2022.107780
Mencarini, L., Vestito, A., Montagnani, M., & Zagari, R. M. (2024). New Developments in the Ultrasonography Diagnosis of Gallbladder Diseases. Gastroenterology Insights, 15(1), 42–68. https://doi.org/10.3390/gastroent15010004
Ng, W. K., & Ng, W. F. (1995). Elevated serum alpha-fetoprotein in a patient with undifferentiated carcinoma of the gall bladder. Journal of clinical pathology, 48(11), 1061-1063.
Potapovich, A. I., Pastore, S., Kostyuk, V. A., Lulli, D., Mariani, V., De Luca, C., Dudich, E. I., & Korkina, L. G. (2009). alpha-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes. British journal of pharmacology, 158(5), 1236–1247. https://doi.org/10.1111/j.1476-5381.2009.00401.x
Rajab, I. M., Addams, J. M. B., Nelson, M. S., Potempa, L. A., Olson, M. E., Choe, M. L., & Majerczyk, D. (2020). C-reactive protein in gallbladder diseases: diagnostic and therapeutic insights. Biophysics Reports, 6(2–3), 49–67. https://doi.org/10.1007/s41048-020-00108-9
Ramesh, O., Gupta, M., Kaushik, S., Acharya, S., Thakur, B., & Bhardwaj, A. (2024). Study of morphology with assessment of expression of proliferation marker Ki67 antigen and P53 protein in lesions of gall bladder. Indian Journal of Pathology and Microbiology, 67(2), 367-373.
Raziq, S. S. S. A. H., & Ahmed, K. M. (2016). Ki 67 Expression in various diseases of gallbladder. Medical Journal of Babylon, 13(3), 712-721.
Raziq, S. S. S. A. H., & Ahmed, K. M. (2016). Ki 67 Expression in various diseases of gallbladder. Medical Journal of Babylon, 13(3), 712-721.
Roa, I., De Aretxabala, X., Araya, J. C., & Roa, J. (2006). Preneoplastic lesions in gallbladder cancer. Journal of surgical oncology, 93(8), 615-623.
Scholzen, T., & Gerdes, J. (2000). The Ki-67 protein: from the known and the unknown. Journal of Cellular Physiology, 182(3), 311–322. https://doi.org/10.1002/(sici)1097-4652(200003)182:3<311::aid-jcp1>3.0.co;2-9Sethi, H., & Johnson, C. D. (2011). Gallstones. Medicine, 39(10), 624-629.
Singh, V., Yadav, A., Sharma, S. P., & Verma, N. (2018). Frequency of histopathological changes in gall bladder mucosa associated with gallstones. Journal of the Anatomical Society of India, 67, S10-S13.
Sood, S., Kumar, R., Varshney, A., Sharma, V. K., Mohan, A., Wadhwa, B., & Kamini, K. (2016). A Histopathological Study of Non Neoplastic Gall Bladder Diseases with Special Reference to Mucin Histochemistry. Annals of applied bio-sciences, 3(2), A189-195
Stroup, D., Crestani, M., & Chiang, J. (1997). Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A. The American Journal of Physiology, 273(2 Pt 1), G508–G517. https://doi.org/10.1152/ajpgi.1997.273.2.g508
Tanno, S., Fujii, T., Shudo, R., Obara, T., Ura, H., Mizukami, Y., Nishino, N., Klein-Szanto, A. J. P., & Kohgo, Y. (1998). Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union. Cancer, 83(2), 267–275. https://doi.org/10.1002/(sici)1097-0142(19980715)83:2<267::aid-cncr10>3.0.co;2-r
Vakkala, M., Laurila, J. J., Saarnio, J., Koivukangas, V., Syrjälä, H., Karttunen, T., ... & Ala-Kokko, T. I. (2007). Cellular turnover and expression of hypoxic-inducible factor in acute acalculous and calculous cholecystitis. Critical Care, 11, 1-6.
Yeo, Y. H., You, S., Tseng, H.-R., Yang, J. D., Tseng, H.-R., Yang, J. D., You, S., Zhu, Y., Zhu, Y., Lee, Y.-T., Zhu, Y., Agopian, V. G., & Yang, J. D. (2024). Alpha-fetoprotein: Past, present, and future. Hepatology Communications, 8(5). https://doi.org/10.1097/hc9.0000000000000422
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
