Loss of tumor suppressor menin expression in high grade cholangiocarcinomas

Terry C Lairmore; Jehan Abdulsattar; Arrigo De Benedetti; Runhua Shi; Shile Huang; Md Imtiaz Khalil; Stephan N Witt

doi:10.1186/s13104-023-06282-6

Loss of tumor suppressor menin expression in high grade cholangiocarcinomas

BMC Res Notes. 2023 Feb 13;16(1):15. doi: 10.1186/s13104-023-06282-6.

Authors

Terry C Lairmore^{1

2

3}, Jehan Abdulsattar⁴, Arrigo De Benedetti^{5

6}, Runhua Shi⁵, Shile Huang^{5

6}, Md Imtiaz Khalil⁶, Stephan N Witt^{7

8}

Affiliations

¹ Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. terry.lairmore@lsuhs.edu.
² Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. terry.lairmore@lsuhs.edu.
³ Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. terry.lairmore@lsuhs.edu.
⁴ Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
⁵ Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
⁶ Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
⁷ Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. stephan.witt@lsuhs.edu.
⁸ Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. stephan.witt@lsuhs.edu.

Abstract

Background: MEN1, which codes for the protein menin, is a tumor suppressor in neuroendocrine tissue. In cholangiocarcinoma (CCA) cell lines the overexpression of menin decreased proliferation, angiogenesis, migration, and invasion in vitro and in xenografts, but its expression in CCA tumor tissue samples is not established.

Objective: Determine whether the expression of menin correlates with disease progression in patient samples of CCA in a tissue microarray (TMA) by immunohistochemical (IHC) staining.

Results: IHC analysis of 97 biopsies revealed that low-grade tumors (Grade I) exhibited intense, diffuse, finely granular nuclear menin immunoreactivity with a pronounced linear perinuclear pattern (mean IHC score = 2.00), whereas high-grade tumors (Grade III) mostly lacked such staining (mean IHC score = 0.35). Collectively, there was a significant inverse association between tumor grade and menin staining (P = 0.0005). We also found a significant association between fibrosis status and menin staining, in that, 81.2% (56/69) of patients without fibrosis had no menin staining, whereas 92.9% (26/28) patients with fibrosis exhibited menin staining (P < 0.0001). No association was found between fibrosis status and grade. Overall, menin expression is inversely associated with tumor grade and positively associated with fibrosis status.

Keywords: Cholangiocarcinoma; Fibrosis; Menin; Tumor suppressor.

MeSH terms

Bile Duct Neoplasms*
Bile Ducts, Intrahepatic
Biopsy
Cholangiocarcinoma* / genetics
Humans
Transcription Factors

Substances

Transcription Factors