Abstract
Nuclear atypia is one of the most important morphological features used to diagnose malignant neoplasms. The potential molecular alteration that causes nuclear atypia remains unknown. P53 and p16INK4A play crucial roles in cell cycle checkpoints and repairing DNA damage to maintain integrity of the genome. Thus, inactivation of p53 and p16INK4A has been hypothesized to alter the chromatin structure and result in nuclear atypia. This study examined 201 primary lung cancers for the immunohistochemical expression of p53 and p16INK4A, and analyzed potential associations with the essential elements of nuclear atypia, such as nuclear size, circularity of the outline, and the density and granularity of chromatin. Tumors that expressed high levels of p53 had larger nuclei with higher chromatin density and distorted nuclear outlines. Tumors that expressed low levels of p16INK4 had larger nuclei with distorted nuclear outlines. Thus, alterations in p53 and p16INK4A may be the potential cause of nuclear atypia in neoplastic cells.
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Acknowledgments
This work was supported by the Japanese Ministry of Education, Culture, Sports, and Science (Tokyo Japan), and by a grant from Smoking Research foundation (Tokyo, Japan). We especially thank Emi HONDA and Misa OTARA (Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan), and Hideaki MITSUI (Yokohama City University School of Medicine, Yokohama, Japan) for their assistance.
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Okudela, K. An association between nuclear morphology and immunohistochemical expression of p53 and p16INK4A in lung cancer cells. Med Mol Morphol 47, 130–136 (2014). https://doi.org/10.1007/s00795-013-0052-x
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DOI: https://doi.org/10.1007/s00795-013-0052-x