ABSTRACT
The objective of this study was to determine the frequency of expression of GRP78 and BIK/NBK proteins, as well as to evaluate their correlation with prognostic factors for clinical use in patients with locally advanced breast cancer (LABC) or preoperative chemotherapy (PC). An observational, analytical and retrospective study that evaluated the expression of BIK/NBK and GRP78 by means of immunohistochemistry in paraffin-embedded tumour tissue samples obtained before the start of PC was executed. GRP78 was positive in 93.3% and BIK/NBK was positive in 40% of the samples analysed. Correlation of GRP78 expression with Ki67 expression (Rho = 0.732, p = .039), and of BIK/NBK expression with Ki67 expression (Rho = 0.777, p = .023) and number of residual lymph nodes (Rho = 0.619, p = .014) was observed. Given the correlation observed, association studies of the expression of GRP78 and BIK/NBK with clinical and pathological response, recurrence and survival should be carried out in a greater number of patients with LABC or PC.Impact StatementWhat is already known on this subject? There are reports of the overexpression of GRP78 in various types of cancer cell lines and tumour biopsies, including breast cancer, with participation in resistance to adjuvant chemotherapeutic agents (topoisomerase inhibitors including Adriamycin). On the other hand, BIK/NBK has been observed expressed associated with poor outcomes in breast cancer. There are no studies of the expression of both biomarkers in patients with preoperative chemotherapy, including locally advanced breast cancer (LABC) or their correlation with prognosis markers of clinical use.What the results of this study add? We observed a correlation of higher expression percentage of GRP78 and BIK/NBK with higher expression of Ki67, a marker of poor prognosis in breast cancer, in addition to a significant correlation of higher percentage of BIK/NBK expression with a greater number of residual nodes in patients with LABC or PC.What the implications are of these findings for clinical practice and/or further research? There is a potential prognostic value of GRP78 and BIK/NBK in the pathological response that merits further study addressing their interaction with other proteins, their cellular location in relation to the clinical stages of breast cancer, and their association with prognosis (clinical and pathological response, recurrence, disease free period and survival) in a greater number of patients with LABC or PC.
Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis Regulatory Proteins/analysis , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Heat-Shock Proteins/analysis , Mitochondrial Proteins/analysis , Adult , Aged , Biomarkers, Tumor/analysis , Chemotherapy, Adjuvant , Endoplasmic Reticulum Chaperone BiP , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Ki-67 Antigen/analysis , Middle Aged , Neoadjuvant Therapy , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
Background: In Mexico, breast cancer (BCa) is in first place regarding cancer mortality and has been established as a priority health issue. The incidence of metastasis from BCa is very high and presents as the principal mortality factor among women younger than 40 years of age. OBJECTIVE. To determine any associations between clinicopathological characteristics and metastasis in Mexican women under 40 years of age. Methods: During the 20102015 period, a total of 180 female BCa cases seen at the Navy General High Specialty Hospital, SEMAR, in Mexico City; we collected information on 20 patients with BCa younger than 40 years of age. Statistical analyses were conducted using the KolmogorovSmirnov, Students t, Fisher, Chi square, and MantelHaenszel tests. Results: The prevalence of women with BCa younger than the age of 40 years during the 20102015 period was 13.3%. We found a high frequency of obesity in of these cases (>75%); 100% of obese patients with a history of smoking presented with metastasis (p <0.05). In addition, the hormone phenotype was important; HER2-positive cases were 12 times more likely tto exhibit metastasis (p <0.05), while expression of estrogen and progesterone receptors appeared to be protective. Diabetes mellitus in combination with smoking was also a risk factor for development of metastasis (p <0.05). Conclusion: In this study, we obtained essential data regarding risk of metastasis in young breast cancer cases which could be useful for predicting disease evolution and treatment response.