An Algorithm-based Technique for Counting Mitochondria in Cells Using Immunohistochemical Staining of Formalin-fixed and Paraffin-embedded Sections

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Apr 2

PMID 38565653

Authors

Mai Sakashita

Noriko Motoi

Gaku Yamamoto

Emi Gambe

Masanori Suzuki

Yukihiro Yoshida

Shun-Ichi Watanabe

Yutaka Takazawa

Kazunori Aoki

Atsushi Ochiai

Shingo Sakashita

Affiliations

Soon will be listed here.

Abstract

Purpose: Visualizing mitochondria in cancer cells from human pathological specimens may improve our understanding of cancer biology. However, using immunohistochemistry to evaluate mitochondria remains difficult because almost all cells contain mitochondria and the number of mitochondria per cell may have important effects on mitochondrial function. Herein, we established an objective system (Mito-score) for evaluating mitochondria using machine-based processing of hue, saturation, and value color spaces.

Methods: The Mito-score was defined as the number of COX4 (mitochondrial inner membrane) immunohistochemistry-positive pixels divided by the number of nuclei per cell. The system was validated using four lung cancer cell lines, normal tissues, and lung cancer tissues (199 cases).

Results: The Mito-score correlated with MitoTracker, a fluorescent dye used to selectively label and visualize mitochondria within cells under a microscope (R = 0.68) and with the number of mitochondria counted using electron microscopy (R = 0.79). Histologically, the Mito-score of small cell carcinoma (57.25) was significantly lower than that of adenocarcinoma (147.5, p < 0.0001), squamous cell carcinoma (120.6, p = 0.0004), and large cell neuroendocrine carcinoma (111.8, p = 0.002).

Conclusion: The Mito-score method enables the analysis of the mitochondrial status of human formalin-fixed paraffin-embedded specimens and may provide insights into the metabolic status of cancer.

Citing Articles

Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients.

Sugawara K, Sakashita S, Fukuda T, Murakami C, Oka D, Amori G Ann Surg Oncol. 2024; 32(3):1963-1972.

PMID: 39645554 PMC: 11811432. DOI: 10.1245/s10434-024-16533-w.

ASO Author Reflections: Clinical Relevance of Mitochondrial Status in Patients with Esophageal Squamous Cell Carcinoma.

Sugawara K, Sakashita S, Motoi N Ann Surg Oncol. 2024; 32(3):1987-1988.

PMID: 39623186 DOI: 10.1245/s10434-024-16573-2.

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