Is Gallbladder Adenomyomatosis a Precancerous Lesion? Comparison of Ki-67 and P53 Positive Expression with Normal Gallbladder Tissue

Year 2022, Issue: 18, 1041 - 1051, 31.12.2022

Veysi Hakan Yardımcı Süheyla Ekemen Abdullah Yüksel Barut

https://doi.org/10.38079/igusabder.1033234

Abstract

Aim: The exact pathogenesis of gallbladder adenomyomatosis (GBA) is still not fully elucidated, and there is some controversy regarding its diagnosis and treatment. Adenomyomatosis, which was initially considered a precancerous lesion, has been recognized in recent studies as a benign alteration of the gallbladder often associated with cholecystitis and cholecystolithiasis. In this study, to investigate the pathogenesis of GBA; It was aimed to compare the levels of biomarkers showing the proliferative activity of tumor cells in normal and adenomyomatosis tissue of the gallbladder and the levels of biomarkers showing the positivity pattern of neoplastic tissue in the same patient.

Method: The pathology reports of a total of 750 patients who underwent laparoscopic cholecystectomy between 2019-2020 were reviewed, and 20 cases diagnosed with adenomyomatosis were evaluated retrospectively. Ki-67 as a proliferation marker and P53 as a neoplastic activity marker were evaluated separately in the normal tissue of the gallbladder and adenomyomatosis tissue.

Results: When the mean values of the Ki-67 index in the normal gallbladder and adenomyomatosis tissue were compared, a statistically significant difference was found (p<0,000). However, when these two groups were compared in terms of the mean values of the P53 index, no statistical difference was found (p=0,062).

Conclusion: Although this study found significantly higher Ki-67 proliferation marker levels in adenomyomatosis tissues, the fact that the common P53-positivity pattern of gallbladder cancer did not show significant differences in these tissues compared to normal tissues appears to support that GBA is not a cancer-precursor lesion but a benign proliferative lesion.

Keywords

Gallbladder adenomyomatosis, gallbladder cancer; P53, proliferative marker, neoplastic marker, Safra kesesi adenomyomatozisi, safra kesesi kanseri, P53, Ki-67, proliferatif belirteç, neoplastik belirteç

Safra Kesesi Adenomyomatozisi Prekanseröz Lezyon mudur? Ki-67 ve P53 Pozitif Ekspresyonunun Normal Safra Kesesi Dokusu ile Karşılaştırılması

Abstract

Amaç: Safra kesesi adenomyomatozisinin (SKA) kesin patogenezi hala tam olarak açıklanamamıştır, tanı ve tedavisine ilişkin bazı tartışmalar mevcut. Başlangıçta kanser öncesi bir lezyon olarak kabul edilen adenomyomatozis, son zamanlarda yapılan çalışmalarda safra kesesinin sıklıkla kolesistit ve kolelitiazis ile ilişkili iyi huylu bir değişikliği olarak kabul edilmektedir. Bu çalışmada, SKA patogenezini araştırmak için; aynı hastada safra kesesi normal ve adenomyomatozis dokusunda, tümör hücrelerinin proliferatif aktivitesini gösteren biyobelirteç düzeyleri ve neoplastik doku pozitiflik paternini gösteren biyobelirteç düzeylerinin karşılaştırılması amaçlanmıştır.
Yöntem: 2019-2020 yılları arasında toplam 750 laparoskopik kolesistektomi uygulanan hastanın patoloji raporları incelenmiş, adenomyomatozis tanısı alan 20 vaka retrospektif olarak değerlendirilmiştir. Proliferasyon belirteci olarak Ki-67 ve neoplastik aktivite belirteci olarak P53, safra kesesi normal dokusu ile adenomyomatozis dokusunda ayrı ayrı değerlendirilmiştir.
Bulgular: Safra kesesi normal ve adenomyomatozis dokusundaki Ki-67 indeksi ortalama değerleri karşılaştırıldığında, istatistiksel olarak anlamlı fark bulundu (p<0,000). Ancak bu iki grup P53 indeksi ortalama değerleri açısından karşılaştırıldığında istatistiksel fark bulunamadı (p=0,062).
Sonuç: Çalışmada adenomyomatozis dokularında anlamlı derecede yüksek Ki-67 proliferasyon belirteci düzeyleri tespit edilmesine karşın, safra kesesi kanserinin yaygın P53-pozitiflik paterninin bu dokularda normal dokularla karşılaştırıldığında anlamlı farklar saptanmaması, SKA’nin kanser öncüsü bir lezyon olmayıp, iyi huylu proliferatif bir değişiklik olduğunu destekler görünmektedir.

Keywords

Safra kesesi adenomyomatozisi, safra kesesi kanseri, P53, Ki-67, proliferatif belirteç, neoplastik belirteç

References

• Van Breda Vriesman AC, Engelbrecht MR, Smithuis RH, Puylaert JB. Diffuse gallbladder wall thickening: Differential diagnosis. Am J Roentgenol. 2007;188(2):495-501.
• Dong Y, Xu B, Cao Q, et al. Incidentally detected focal fundal gallbladder wall thickening: Differentiation contrast enhanced ultrasound features with high-resolution linear transducers. Clin Hemorheol Microcirc. 2020;74(3):315-325.
• Mahajan A, Sripathi S. Gallbladder Adenomyomatosis Mimicking Carcinoma: A Diagnostic Dilemma. J Glob Oncol. 2016;2(5):341-345.
• Pang L, Zhang Y, Wang Y, Kong J. Pathogenesis of gallbladder adenomyomatosis and its relationship with early-stage gallbladder carcinoma: An overview. Braz J Med Biol Res. 2018;51(6):e7411.
• Cavallaro A, Piccolo G, Panebianco V, et al. Incidental gallbladder cancer during laparoscopic cholecystectomy: Managing an unexpected finding. World J Gastroenterol. 2012;18(30):4019-4027.
• Fuks D, Regimbeau JM, Le Treut YP, et al. Incidental gallbladder cancer by the AFC-GBC-2009 Study Group. World J Surg. 2011;35(8):1887-1897.
• Kai K, Aishima S, Miyazaki K. Gallbladder cancer: Clinical and pathological approach. World J Clin Cases. 2014;2(10):515-521.
• Morikawa T, Okabayashi T, Shima Y, et al. Adenomyomatosis Concomitant with Primary Gallbladder Carcinoma. Acta Med Okayama. 2017;71(2):113-118.
• Kai K, Ide T, Masuda M, et al. Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis. Virchows Arch. 2011;459(6):573-580.
• Suzuki K, Abe K, Ohbu M. A Resected Gallbladder Carcinoma Coexisting With Adenomyomatosis Involving Varied Degrees of Intraepithelial Dysplasia: A Case Report and Literature Review. Surg Laparosc Endosc Percutan Tech. 2019;29(4):290-296.
• Yu MH, Kim YJ, Park HS, Jung SI. Benign gallbladder diseases: Imaging techniques and tips for differentiating with malignant gallbladder diseases. World J Gastroenterol. 2020;26(22):2967-2986.
• Golse N, Lewin M, Rode A, Sebagh M, Mabrut JY. Gallbladder adenomyomatosis: Diagnosis and management. J Visc Surg. 2017;154(5):345-353.
• Yoon JH, Cha SS, Han SS, Lee SJ, Kang MS. Gallbladder adenomyomatosis: imaging findings. Abdom Imaging. 2006;31(5):555-563.
• Runner GJ, Corwin MT, Siewert B, Eisenberg RL. Gallbladder wall thickening. Am J Roentgenol. 2014;202(1):W1-W12.
• Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol. 2017;23(22):3978-3998.
• Niu ZS, Niu XJ, Wang M. Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival. World J Hepatol. 2015;7(1):7-27.
• Jiang YH, Cheng B, Ge MH, Zhang G. The prognostic significance of p63 and Ki-67 expression in myoepithelial carcinoma. Head Neck Oncol. 2012;4:9-15.
• Shu GS, Lv F, Yang ZL, Miao XY. Immunohistochemical study of PUMA, c-Myb and p53 expression in the benign and malignant lesions of gallbladder and their clinicopathological significances. Int J Clin Oncol. 2013;18(4):641-650.
• Katabi N, Pillarisetty VG, DeMatteo R, Klimstra DS. Choledochal cysts: a clinicopathologic study of 36 cases with emphasis on the morphologic and the immunohistochemical features of premalignant and malignant alterations. Hum Pathol. 2014;45(10):2107-2114.
• Wee A, Teh M, Raju GC. Clinical importance of p53 protein in gall bladder carcinoma and its precursor lesions. J Clin Pathol. 1994;47(5):453-456.
• Itoi T, Watanabe H, Ajioka Y, et al. APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis. Pathol Int. 1996;46(5):333-340.
• Nabatame N, Shirai Y, Nishimura A, et al. High risk of gallbladder carcinoma in elderly patients with segmental adenomyomatosis of the gallbladder. J Exp Clin Cancer Res. 2004;23(4):593-598.