Abstract

BackgroundInvasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial. Enhancer of Zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), is frequently overexpressed in various cancers. This study evaluated the relationship between clinicopathologic characteristics and EZH2 expression.MethodsWe retrospectively reviewed the medical records of 54 patients with ILC and selected 49 cases of ILC. Immunohistochemistry for EZH2 was undertaken.ResultsWe defined ILC as discohesive cells with a linear or nonlinear growth pattern. No statistically significant difference was found for most variables, including multifocality, menstrual status, body mass index, tumor stage (pT), lymph node stage (pN), estrogen receptor, and progesterone receptor. In contrast, nuclear grade was statistically significant and EZH2 expression was associated with high nuclear grade. In total, 80% of nuclear grade 3 cases had an EZH2 score of 4, and 86% of nuclear grade 1 cases had EZH2 scores of 1 and 2. Our cases had a score of 3 for tubule formation and a score of 1 for mitosis, and so the histologic grading consisted of grades 1 (7 cases) and 2 (42 cases) depending on the nuclear grade.ConclusionAlthough EZH2 could not predict survival in our study, EZH2 expression was associated with a high nuclear grade. Most ILCs have histologic grade 2 with nuclear grade 2 or 3. Therefore, our opinion is that if ILC is diagnosed by separating the classic type and variants and considering both EZH2 expression and nuclear grade, EZH2 overexpression could help and the Nottingham grading system would be more accurate prognostic factor.

Highlights

  • Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial

  • Our opinion is that if ILC is diagnosed by separating the classic type and variants and considering both Enhancer of Zeste homolog 2 (EZH2) expression and nuclear grade, EZH2 overexpression could help and the Nottingham grading system would be more accurate prognostic factor

  • 49 cases were scored for expression of EZH2 and the remaining cases were excluded from further analyses because of insufficient tumor size or due to artifacts

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Summary

Introduction

Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial. Enhancer of Zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), is frequently overexpressed in various cancers. Invasive lobular carcinoma (ILC) was first described by Foot and Stewart [1] in 1941 and is the second most common histologic type of breast cancer, comprising 5% to 15% of newly diagnosed invasive tumors. EZH2 plays an essential role in epigenetic maintenance and is frequently overexpressed in a wide variety of cancerous tissue types. It is associated with poor prognosis for prostate cancer [5] and other malignancies [6,7]

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