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The Pathologist / Issues / 2025 / October / p63 Immunohistochemistry May Skew Breast Cancer Diagnosis
Oncology Research and Innovations Molecular Pathology

p63 Immunohistochemistry May Skew Breast Cancer Diagnosis

Researchers show that p63 expression occurs in most high-grade invasive breast carcinomas.

10/03/2025 News 2 min read

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Credit: Adobe Stock (edited)

p63 expression was identified in 80 percent of high-grade invasive breast carcinomas, whereas low- and intermediate-grade tumors showed little to no expression, according to a recent study.

p63 is a well-established nuclear marker of myoepithelial cells and is routinely used in breast pathology to differentiate in situ from invasive carcinoma. Invasive carcinoma cells are conventionally negative for p63, and its absence is taken as evidence of stromal invasion. Researchers evaluated p63 expression in tumor cells of invasive breast carcinoma of no special type to determine whether grade-specific differences exist.

The study, published in Annals of Diagnostic Pathology, included 60 core biopsies, with 20 cases each of Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors, classified according to the Nottingham grading system. Immunohistochemical staining was performed with a monoclonal anti-p63 antibody, and nuclear expression in invasive tumor cells was recorded. Sixteen of 20 G3 carcinomas (80 percent) showed focal nuclear p63 expression, involving 1 percent to 20 percent of tumor cells, with staining intensity reported as weak in 6 cases and moderate in 10. Among G2 carcinomas, 2 of 20 cases (10 percent) exhibited weak focal positivity, while the remaining 18 were negative. All G1 carcinomas demonstrated negativity for p63 in the invasive component.

The findings indicate a clear association between p63 expression in tumor cells and higher histologic grade. The researchers note that p63 staining in invasive tumor cells is most often focal and of limited intensity, without strong or diffuse patterns. This pattern was not observed in low-grade carcinomas and was only rarely identified in intermediate-grade carcinomas.

The results highlight a potential diagnostic consideration when interpreting core biopsies, particularly in cases where p63 positivity may be mistakenly attributed to residual myoepithelial cells. The researchers also note that the presence of p63 in tumor cells appears more frequent in G3 carcinomas, with focal staining occurring across molecular subtypes including triple-negative, Luminal B, and HER2-enriched tumors.

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