Heterogeneous Intermediate Phenotypes of Cancer Cells with Varying Ki-67-Positivity Rates, Including Histologically...

Area of Science:

• Hepatobiliary pathology
• Cancer cell biology
• Tumor heterogeneity

Background:

• Mixed hepatocellular carcinoma (HCC)-neuroendocrine carcinoma (NEC) represents a significant subtype of liver mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN).
• Primary liver NEC is rare and often co-occurs with HCC.

Purpose of the Study:

• To characterize the cancer cell heterogeneity within HCC and NEC components of liver MiNEN.
• To investigate the potential cellular origins and differentiation pathways in mixed HCC-NEC.

Main Methods:

• Comprehensive analysis of protein expression for TERT, Ki-67, p53, hepatocyte, and neuroendocrine markers.
• Utilized immunohistochemistry and immunofluorescence on resection tissues from three liver MiNEN patients.

Main Results:

• TERT, Ki-67, and p53 proteins showed distinct expression patterns in HCC and NEC components, with higher overall expression in NEC.
• Ki-67 was highly expressed in both components.
• Intermediate cell phenotypes (HCC-like and NEC-like) were identified, particularly within the HCC component, suggesting a potential transdifferentiation process from HCC to NEC.

Conclusions:

• The similar expression signatures of proliferation markers between HCC and NEC components suggest a possible common origin.
• Evidence supports a model where HCC cells may dedifferentiate and transdifferentiate into NEC cells in mixed HCC-NEC.
• Understanding this heterogeneity is crucial for diagnosing and treating liver MiNEN.