ABSTRACT
Objective:To investigate the correlation of PELP1/MNAR expression with expressions of estrogen receptor (ER), Ki-67, human epidermal growth factor receptor 2 (HER2) and PIK3CA gene mutation.Methods:A total of 80 paraffin-embedded tissue specimens of primary invasive breast cancer patients in the Fifth People's Hospital of Datong in Shanxi Province from January 2008 to December 2018 were collected. The expression of PELP1/MNAR was examined by immunohistochemistry EliVision tow-step method. The polymerase chain reaction (PCR)-Sanger sequencing method was used to detect the mutation of PIK3CA gene. The expressions of PELP1/MNAR among patients with different expression status of ER, Ki-67, HER2 and with or without PIK3CA gene mutation were compared, and the correlations between each index and the expression of PELP1/MNAR were analyzed.Results:The high expression rates of PELP1/MNAR protein in patients with ER-positive [86.1% (31/36) vs. 59.1% (26/44)], Ki-67 high expression [100.0% (13/13) vs. 65.7% (44/67)], HER2-positive [81.0% (34/42) vs. 60.5% (23/38)] were high, and the differences were statistically significant (all P<0.05). There was no significant difference in the high expression rate of PELP1/MNAR protein between patients with mutant and wild-type PIK3CA [60.0% (12/20) vs. 75.0% (45/60), P = 0.199]. The expression of PELP1/MNAR was negatively correlated with the expression level of ER ( r = -0.195, P < 0.05), positively correlated with the expression level of Ki-67 ( r = 0.198, P < 0.05), positively correlated with the expression level of HER2 ( r = 0.225, P < 0.05), and negatively correlated with lymph node metastasis ( r = -0.269, P < 0.05). Conclusions:The expression of PELP1/MNAR in invasive breast cancer is negatively correlated with the expression level of ER, and positively correlated with the expression level of Ki-67 and HER2. There is no correlation between PELP1/MNAR expression and PIK3CA gene mutation, and the two may play their own role in the PI3K-AKT-mTOR regulatory pathway of breast cancer.
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.