DIAGNOSTIC ROLE OF IMMUNOMARKER EXPRESSIONS IN GALLBLADDER CARCINOMA AND PREMALIGNANT LESIONS
Main Article Content
Keywords
Cyclin D1, E-cadherin, EGFR, HER- 2, Ki67, p53 tumor marker, neoplastic, ,non -neoplastic Gall bladder lesions
Abstract
Abstract:
Background: Worldwide gall bladder cancer (GBC) is known to be the commonest malignant tumour of the biliary tract .It is the most aggressive carcinoma of the biliary tract with short median survival from the time of diagnosis. The aggressive biologic behavior of the carcinoma and non-availability of sensitive screening tests for early detection may be responsible for the poor prognosis associated with GBC. Owing to the delayed diagnosis at an advanced stage, only 10% of the patients are found to be eligible for a curative surgical resection.
Material and Methods: All consecutive patients diagnosed with neoplastic and non-neoplastic gallbladder lesions in the Department of Pathology, Subharti Medical College were included in the study between the year 2017 -2019. The hematoxylin and Eosin stained biopsies of 320 patients were assessed and out of them 100 patients were chosen as the sample for the study. The clinicopathological data of the 100 patients were compiled into a data base and de-identified.
Results: Age distribution of Gall Bladder lesion cases in our study was from 30 years to more than 60 years of age. 46.20% of females in the age group of 45 years to 60 years presented with mass in the gall bladder. Overall, the concordance rates between the immunomarkers was relatively high, ranging from 47% to 88% except between E-cadherin and other immunomarkers. This suggests that the immunomarkers are generally related to each other. The high concordance rate was found between p53 and Ki67, p53 and EGFR, p53 and Cyclin D1, Ki67 and EGFR, Ki67 and Cyclin D1 , EGFR and Cyclin D1., EGFR, HER2/neu and Cyclin D1.
Conclusions: The minimal response of advanced cases of GBC to traditional treatments calls for new prognostic and treatment perspectives to be identified. Novel prognostic biomarkers could bring about the needed breakthrough in this regard as they will help in the identification of patients who will benefit tremendously from adjuvant and targeted therapies.
References
2. Kanthan R, Senger JL, Ahmed S, Kanthan SC. Gallbladder Cancer in the 21st Century. J Oncol. 2015; 2015:967472. doi: 10.1155/2015/967472. Epub 2015 Sep 1. PMID: 26421012; PMCID: PMC4569807.
3. Mochidome N, Koga Y, Ohishi Y, Miyazaki T, Matsuda R, Yamada Y, Aishima S, Nakamura M, Oda Y. Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer. Hum Pathol. 2021 Aug; 114: 44-53. doi: 10.1016/j.humpath.2021.05.001. Epub 2021 May 11. PMID: 33989638.
4. Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol. 2017 Jun 14; 23 (22):3978-3998. doi: 10.3748/wjg.v23.i22.3978. PMID: 28652652; PMCID: PMC5473118.
5. Cui X, Zhu S, Tao Z, Deng X, Wang Y, Gao Y, Liao Y, Ma W, Zhang Y, Ma X. Long-term outcomes and prognostic markers in gallbladder cancer. Medicine (Baltimore). 2018 Jul; 97 (28):e11396. doi: 10.1097/MD.0000000000011396. PMID: 29995783; PMCID: PMC6076111.
6. Rawla P, Sunkara T, Thandra KC, Barsouk A. Epidemiology of gallbladder cancer. Clin Exp Hepatol. 2019 May; 5 (2):93-102. doi: 10.5114/ceh.2019.85166. Epub 2019 May 23. PMID: 31501784; PMCID: PMC6728871.
7. Mishra SK, Kumari N, Krishnani N. Molecular pathogenesis of gallbladder cancer: An update. Mutat Res. 2019 Nov; 816-818:111674. doi: 10.1016/j.mrfmmm.2019.111674. Epub 2019 Jul 6. PMID: 31330366.
8. Montalvo-Jave EE, Rahnemai-Azar AA, Papaconstantinou D, Deloiza ME, Tsilimigras DI, Moris D, Mendoza-Barrera GE, Weber SM, Pawlik TM. Molecular pathways and potential biomarkers in gallbladder cancer: A comprehensive review. Surg Oncol. 2019 Dec; 31: 83-89. doi: 10.1016/j.suronc.2019.09.006. Epub 2019 Sep 13. PMID: 31541911.
9. Dwivedi AN, Jain S, Dixit R. Gallbladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread. World J Clin Cases. 2015 Mar 16; 3 (3):231-44. doi: 10.12998/wjcc.v3.i3.231. PMID: 25789296; PMCID: PMC4360495.
10. Liu Z, Jin H, Yang S, Cao H, Zhang Z, Wen B, Zhou S. SDC1 knockdown induces epithelial-mesenchymal transition and invasion of gallbladder cancer cells via the ERK/Snail pathway. J Int Med Res. 2020 Aug;48 (8):300060520947883. doi: 10.1177/0300060520947883. PMID: 32812461; PMCID: PMC7441293.
11. Verma, K., Dixit, R., Singh, J., Tiwary, S. K., Khanna, A. K., Narayan, G., & Kumar, P. Molecular genetics changes in gallbladder carcinoma. International Journal of Molecular & Immuno Oncology.2020; 5(2): 49-61. doi:10.25259/IJMIO_19_2019
12. Alabi A, Arvind AD, Pawa N, Karim S, Smith J. Incidental Gallbladder Cancer: Routine versus Selective Histological Examination After Cholecystectomy. Surg J (N Y). 2021 Feb 1; 7(1):e22-e25. doi: 10.1055/s-0040-1722175. PMID: 33542953; PMCID: PMC7850885.
13. Saxena, Mohiny; Bohara, Sangita; Gupta, Vivek; Goel, Vijay Kumar1. Role of Morphology and Immunohistochemistry in the Diagnosis of Incidental Cancers in Gallstone Disease. Acta Medica International 10(2): p 143-147, Jul–Dec 2023. | DOI: 10.4103/amit.amit_59_23
14. Mehrotra R, Tulsyan S, Hussain S, Mittal B, Singh Saluja S, Singh S, Tanwar P, Khan A, Javle M, Hassan MM, Pant S, De Aretxabala X, Sirohi B, Rajaraman P, Kaur T, Rath GK. Genetic landscape of gallbladder cancer: Global overview. Mutat Res Rev Mutat Res. 2018 Oct-Dec; 778: 61-71. doi: 10.1016/j.mrrev.2018.08.003. Epub 2018 Aug 23. PMID: 30454684.
15. Haq N, Khan BA, Imran M, Akram A, Jamal AB, Bangash F. Frequency of Gallbladder carcinoma in patients with acute and chronic cholecystitis. J Ayub Med Coll Abbottabad. 2014 Apr-Jun; 26(2):191-3. PMID: 25603675.
16. Roa I, de Toro G, Schalper K, de Aretxabala X, Churi C, Javle M. Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients With Advanced Gallbladder Cancer. Gastrointest Cancer Res. 2014 Mar; 7(2):42-8. PMID: 24799970; PMCID: PMC4007675.
17. Srivastava K, Srivastava A, Mittal B. Potential biomarkers in gallbladder cancer: present status and future directions. Biomarkers. 2013 Feb; 18 (1):1-9. doi: 10.3109/1354750X.2012.717105. Epub 2012 Aug 30. PMID: 22931385.
18. Sharada R. Kankonkar, S. V. Joshi, R. R. Deshpande. Significance of tumor markers in cancer of Gallbladder. Open Journal of Immunology. 2013; Vol.3, No.1, 33-36. doi: 10.4236/oji.2013.31005
19. Hui AM, Li X, Shi YZ, Takayama T, Torzilli G, Makuuchi M. Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma. Clin Cancer Res. 2000 Nov; 6 (11):4272-7. PMID: 11106243.
20. Mrouj K, Andrés-Sánchez N, Dubra G, Singh P, Sobecki M, Chahar D, Al Ghoul E, Aznar AB, Prieto S, Pirot N, Bernex F, Bordignon B, Hassen-Khodja C, Villalba M, Krasinska L, Fisher D. Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis. Proc Natl Acad Sci U S A. 2021 Mar 9; 118 (10):e2026507118. doi: 10.1073/pnas.2026507118. PMID: 33658388; PMCID: PMC7958263.
21. Na TY, Schecterson L, Mendonsa AM, Gumbiner BM. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc Natl Acad Sci U S A. 2020 Mar 17; 117(11):5931-5937. doi: 10.1073/pnas.1918167117. Epub 2020 Mar 3. PMID: 32127478; PMCID: PMC7084067.
22. Klimstra DS, Lam AK, Paradis V, Schirmacher P. Tumors of the gallbladder and extrahepatic bile ducts. In: WHO classification of tumors editorial board. Digestive system tumors. Lyon (France): International agency for research on cancer; 2019. WHO classification of tumors series, 5th ed.; vol. 1. p. 265 92.
23. Das C, Mukhopadhyay M, Subba S, Saha AK, Mukhopadhyay B. Role of EGFR and HER-2/NEU Expression in Gallbladder Carcinoma (GBC). J Lab Physicians. 2021 Mar; 13 (1):29-35. doi: 10.1055/s-0041-1726561. Epub 2021 May 19. PMID: 34103877; PMCID: PMC8164917.
24. Rupesh P, Manoj P, Vijay Kumar S. Biomarkers in carcinoma of the gallbladder. Expert Opin Med Diagn. 2008 May; 2(5):511-26. doi: 10.1517/17530059.2.5.511. PMID: 23495740.
25. Kumar N, Khan MA, Kumar N; Rigvardhan; Ranjan R, Hazra N. Epidermal growth factor receptor expression in carcinoma gallbladder: A prospective study in Indian scenario. J Cancer Res Ther. 2016 Apr-Jun; 12 (2):959-62. doi: 10.4103/0973-1482.179063. PMID: 27461681.
26. Hadi R, Pant MC, Husain N, Singhal A, Khurana R, Agarwal GR, Masood S, Awashthi NP. EGFR and HER-2/neu Expression in Gallbladder Carcinoma: An Institutional Experience. Gulf J Oncolog. 2016 Jan; 1 (20):12-9. PMID: 27050174.
27. Kountourakis P, Pavlakis K, Psyrri A, Rontogianni D, Xiros N, Patsouris E, Pectasides D, Economopoulos T. Clinicopathologic significance of EGFR and Her-2/neu in colorectal adenocarcinomas. Cancer J. 2006 May-Jun;12 (3):229-36. doi: 10.1097/00130404-200605000-00012. PMID: 16803682.
28. Kaur D, Agrawal T, Garg T, Sagar S K, Histopathological study of Gallbladder malignancies with special reference to p53 expression. Indian J Pathol Oncol 2020; 7 (1):147-151. https://doi.org/10.18231/j.ijpo.2020.028
29. Gupta V, Maurya MK, Agarwal P, Kumar M, Sagar M, Raghuvanshi S, Gupta S. Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters. Natl J Maxillofac Surg. 2022 May-Aug; 13 (2):208-215. doi: 10.4103/njms.njms_402_21. Epub 2022 Jul 15. PMID: 36051794; PMCID: PMC9426695.
30. Wee A, Teh M, Raju GC. Clinical importance of p53 protein in Gallbladder carcinoma and its precursor lesions. J Clin Pathol. 1994 May; 47 (5):453-6. doi: 10.1136/jcp.47.5.453. PMID: 8027399; PMCID: PMC502025.
31. Yoon HA, Noh MH, Kim BG, Han JS, Jang JS, Choi SR, Jeong JS, Chun JH. Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma. World J Gastroenterol 2011; 17(35): 4023-4030 [PMID: 22046092 DOI: 10.3748/wjg.v17.i35.4023]
32. Singh P, Jain SL, Sakhuja P, Agarwal A. Expression of VEGF-A, HER2/neu, and KRAS in Gallbladder carcinoma and their correlation with clinico-pathological parameters. Indian J Pathol Microbiol. 2021 Oct-Dec; 64 (4):687-692. doi: 10.4103/IJPM.IJPM_248_20. PMID: 34673587.
33. Bhoge A, Khandeparkar SGS, Joshi AR, Gogate B, Kulkarni MM, Bhayekar P. Immunohistochemical Study of MUC1 and MUC5AC Expression in Gallbladder Lesions. J Clin Diagn Res. 2017 Jul; 11(7):EC12-EC16. doi: 10.7860/JCDR/2017/26537.10230. Epub 2017 Jul 1. PMID: 28892903; PMCID: PMC5583907.
34. García P, Rosa L, Vargas S, Weber H, Espinoza JA, Suárez F, Romero-Calvo I, Elgueta N, Rivera V, Nervi B, Obreque J, Leal P, Viñuela E, Aguayo G, Muñiz S, Sagredo A, Roa JC, Bizama C. Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer. Cancers (Basel). 2020 Mar 25; 12 (4):778. doi: 10.3390/cancers12040778. PMID: 32218280; PMCID: PMC7226626.
35. Liu B, Zhang Y, Liao M, Deng Z, Gong L, Jiang J, Lynn L, Wu K, Miao X. Clinicopathologic and prognostic significance of CD24 in gallbladder carcinoma. Pathol Oncol Res. 2011 Mar; 17 (1):45-50. doi: 10.1007/s12253-010-9278-2. Epub 2010 Jun 22. PMID: 20567952.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Anshoo Agarwal
Department of Pathology, Faculty of Medicine, Swami Vivekananda Subharti University, Meerut, India
Rani Bansal
Department of Pathology, Faculty of Medicine, Government Doon Medical College, Dehradun, India
Kavita Chauhan
Department of Pathology, Faculty of Medicine, Swami Vivekananda Subharti University, Meerut, India
Mamta Gupta
Department of Pathology, Faculty of Medicine, Northern Border University, Arar; Saudi Arabia