Cancer Res Treat.  2019 Apr;51(2):706-717. 10.4143/crt.2018.316.

The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes

• Wang X
• Tsang JY
• Lee MA
• Ni YB
• Tong JH
• Chan SK
• Cheung SY
• To KF
• Tse GM

• KMID: 2464416
• DOI: http://doi.org/10.4143/crt.2018.316

Abstract

PURPOSE
Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel nuclear receptor (NR) co-regulator, is highly expressed in breast cancer. We investigated its expression in breast cancer subtypes, in comparison with other breast markers as well as cancers from different sites. Its prognostic relevance with different subtypes and other NR expression was also examined in breast cancers.
MATERIALS AND METHODS
Immunohistochemical analysis was performed on totally 1,944 cancers from six different organs.
RESULTS
PELP1 expression rate was the highest in breast cancers (70.5%) among different cancers. Compared to GATA3, mammaglobin and gross cystic disease fluid protein 15, PELP1 was less sensitive than GATA3 for luminal cancers, but was the most sensitive for non-luminal cancers. PELP1 has low expression rate (<20%) in colorectal cancers, gastric cancers and renal cell carcinomas, but higher in lung cancers (49.1%) and ovarian cancers (42.3%). In breast cancer, PELP1 expression was an independent adverse prognostic factor for non-luminal cancers (disease-free survival [DFS]: hazard ratio [HR], 1.403; p=0.012 and breast cancer specific survival [BCSS]: HR, 1.443; p=0.015). Interestingly, its expression affected the prognostication of androgen receptor (AR). AR(pos)PELP1(lo) luminal cancer showed the best DFS (log-rank=8.563, p=0.036) while AR(neg)PELP1(hi) non-luminal cancers showed the worst DFS (log-rank=9.536, p=0.023).
CONCLUSION
PELP1 is a sensitive marker for breast cancer, particularly non-luminal cases. However, its considerable expression in lung and ovarian cancers may limit its utility in differential diagnosis in some scenarios. PELP1 expression was associated with poor outcome in non-luminal cancers and modified the prognostic effects of AR, suggesting the potential significance of NR co-regulator in prognostication.

Keyword

PELP1; Breast neoplasms; Differential diagnosis; Prognosis; Immunohistochemistry

MeSH Terms

Breast Neoplasms*
Breast*
Carcinoma, Renal Cell
Colorectal Neoplasms
Diagnosis, Differential
Glutamic Acid
Immunohistochemistry
Lung
Lung Neoplasms
Ovarian Neoplasms
Phenobarbital
Prognosis
Proline
Receptors, Androgen
Stomach Neoplasms
Glutamic Acid
Phenobarbital
Proline
Receptors, Androgen

Figure

• 

  Fig. 1. Representative staining of proline, glutamic acid, and leucine-rich protein 1 expression on breast cancers (A, low; B, focal; C, diffuse staining), lung cancers (D, low; E, focal; F, diffuse staining), and ovarian cancers (G, low; H, focal; I, diffuse staining) (×200).

• 

  Fig. 2. Kaplan-Meier analysis of proline, glutamic acid, and leucine-rich protein 1 (PELP1) expression for disease-free survival (DFS) (A, C, E) and breast cancer specific survival (BCSS) (B, D, F) in all cases (A, B), non-luminal (C, D), and luminal (E, F) breast cancer subgroups. PELP1lo, PELP1 low; PELPhi, PELP1 high.

• 

  Fig. 3. Kaplan-Meier analysis for disease-free survival (DFS) (A, C) and breast cancer specific survival (BCSS) (B, D) according to proline, glutamic acid, and leucine-rich protein 1 (PELP1) and androgen receptor (AR) expression level in non-luminal (A, B) and luminal (C, D) subsets. PELP1lo, PELP1 low; PELPhi, PELP1 high.

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