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Cell-in-Cell Structures in Colorectal Cancer: A Proposed Assessment Method and Correlation with Established Poor
Arseniy Potapov1, Ruslan Spashchanskii1, Aleksey Kazakov1,2
1Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603082, Russia.
Journal of Personalized Medicine
|December 24, 2025
Summary
A new method quantifies cell-in-cell (CIC) structures in colorectal cancer (CRC) surgical specimens. These CIC structures are more prevalent at the tumor invasive front, showing weak correlations with some poor prognosis factors.
Area of Science:
- Oncology
- Histopathology
- Cancer Research
Background:
- Cell-in-cell (CIC) structures, where one cell is found inside another, are linked to poor prognosis and treatment resistance in colorectal cancer (CRC).
- Standardized methods for quantifying CIC structures are lacking, hindering their clinical application in CRC research.
Purpose of the Study:
- To develop and validate an adapted method for quantifying CIC structures in colorectal adenocarcinoma surgical specimens.
- To assess the correlation between CIC structures and established adverse prognostic factors in CRC.
Main Methods:
- Analysis of 250 histological slides from 58 colorectal adenocarcinoma patients (pT1-pT4).
- Immunohistochemistry (CK20) for cell identification and CIC visualization.
- Quantitative assessment of CIC structures on H&E stained digital slides using a ×40 objective.
- Correlation analysis with prognostic factors like tumor-stromal ratio, tumor buds, and tumor-infiltrating lymphocytes.
Main Results:
- Homotypic CIC structures (formed by cancer cells) predominated (95%) over heterotypic ones (5%).
- A significant increase in CIC structures was observed at the invasive front (16.7 ± 5.2) compared to the tumor center (1.2 ± 1.3).
- Weak but statistically significant correlations were found between CIC structures and tumor-stromal ratio, tumor buds, and tumor-infiltrating lymphocytes.
Conclusions:
- An adapted method for counting CIC structures in CRC surgical specimens has been established, with defined identification criteria.
- The study confirms a higher prevalence of CIC structures at the invasive front of colorectal tumors.
- Weak correlations suggest CIC structures may be an independent prognostic factor requiring further investigation in CRC.

