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Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis

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Abstract

Background

Esophageal squamous intraepithelial neoplasia (ESIN) as a precursor for invasive carcinoma is classified into low-grade IN (LIN) and high-grade IN (HIN), the latter including carcinoma in situ (CIS). Increasing grades of ESIN are associated with increasing risk of invasive carcinoma, but differentiation among LIN, HIN, and CIS is subjective and challenging. As p63, a member of the p53 family, is known to regulate differentiation and proliferation in epithelial progenitor cells, its expression, along with that of cytokeratin (CK) 14 (basal squamous marker) and Ki-67 (proliferation marker), might be of diagnostic assistance.

Methods

Immunohistochemical staining was performed on endoscopically resected specimens from 69 patients (73 lesions) with ESIN between 2008 and 2010. Specimens having no atypical cells distant from ESIN were defined as negative for IN (NIN).

Results

There were 13 LIN, 29 HIN, and 31 CIS lesions. The size of CIS (mean 20.1 mm) was significantly larger than that of HIN (14.3 mm) or LIN (10.0 mm). Immunolabeling scores (ILS) for p63, p53, CK14, and Ki-67 showed stepwise increase with ESIN progression (NIN vs. LIN and LIN vs. HIN, P < 0.05–0.0001; HIN vs. CIS, P < 0.05–0.001). Mean total ILSs of all four markers were 2.0 for NIN, 4.3 for LIN, 7.4 for HIN, and 9.1 for CIS (P < 0.0001). A cutoff value for total ILS of ≤5 versus ≥6 demonstrated highest sensitivity (96.0%) and specificity (85.7%) in distinguishing HIN from LIN.

Conclusions

This study suggests that p63 and p53 are coordinately upregulated in esophageal squamous carcinogenesis, and assessment of their expression might provide a useful adjunct tool for differential diagnosis of ESIN.

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Acknowledgments

We thank Mr. Hiroshi Abe, Department of Human Pathology, Juntendo University School of Medicine, for his expert technical assistance.

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Authors and Affiliations

  1. Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan

    Hidenae Nakayama & Sumio Watanabe

  2. Department of Human Pathology, Juntendo University School of Medicine, Motomachi building 3F, Hongo 1-1-19, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hidenae Nakayama, Hiroyuki Mitomi, Abdukadir Imamhasan, Shiro Uchida & Takashi Yao

  3. Department of Surgery, Juntendo University School of Medicine, Tokyo, Japan

    Natsumi Tomita & Yoshiaki Kajiyama

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  1. Hidenae Nakayama
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Correspondence to Hiroyuki Mitomi.

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Nakayama, H., Mitomi, H., Imamhasan, A. et al. Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis. Esophagus 9, 1–8 (2012). https://doi.org/10.1007/s10388-011-0302-8

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