Preferential expression of the multidurg‐resistance‐associated protein (MRP) in adenocarcinoma of the lung

Abstract

The expression of multidrug-resistance-associated protein (MRP) was assessed in various types of untreated lung cancer using an immunohistochemical technique. MRP was abundantly expressed in 28 of 59 adenocarcinoma specimens (47%) and its expression was associated with the degree of glandular differentiation of the tumor. MRP expression in well-differentiated adenocarcinomas (56%) was higher than in poorly differentiated adenocarcinomas (22%) (p < 0.01). lower--20% in squamous-cell carcinomas, 20% in large-cell carcinomas and 0% in small-cell carcinomas and carcinoids. RT-PCR showed that the MRP-positive adenocarcinomas and squamous-cell carcinomas expressed mrp mRNA significantly. Immunoelectron microscopically, MRP was localized in the plasma membrane and rough endoplasmic reticulum. It is thus important to take MRP into account when considering chemotherapy for lung cancers because levels of mdr I gene product, another multidrug-resistance gene family, are low in untreated lung cancers.

Multidrug resistance-associated protein (MRP1) is overexpressed in DNA aneuploid carcinomatous cells in non-small cell lung cancer (NSCLC)

“…14,15 Heterogeneous expression of MRP1 has been observed between various NSCLC samples after evaluation by either RNA detection, immunohistochemistry or mRNA evaluation by in situ hybridization, 6,9,23 In these studies, this heterogeneity has been related to tumor histology or differentiation with contradictory results. 6,7,23,25 The present study, based on concomitant analysis of DNA cell content by flow cytometry and MRP1 protein expression, revealed heterogeneous MRP1 expression associated with the DNA ploidy status of tumor cells, and a similar percentage of MRP1-positive cells was observed in SCC and adenocarcinomas. However, the MRP ratio per cell was higher in SCC than in adenocarcinomas, particularly in DNA aneuploid cells.…”

Immunohistochemical detection of DNA topoisomerase IIα, P-glycoprotein and multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer

“…However, when analysing their frequency in subtypes of NSCLC, it is interesting that both our (Table II) and a previous study (Ota et al, 1995) detected an increased level of MRP in SCC relative to other histological subtypes. This was, however, not the case when an mRNA assay was used (Sugarawa et al, 1995), a result which could be due to admixture of MRP mRNA from macrophages and lymphocytes (Thomas et al, 1994;Figure 4). The highly significant difference in topo-Ila content between untreated SCLC and NSCLC (Tables 1 and 2) is therefore remarkable.…”

“…In this respect, a mRNA and/or catalytic assay for topo-Ila should be more dependable as this protein is, for practical purposes, only found in tumour tissue. Both P-gp and MRP have been detected in SCLC and NSCLC, although their clinical importance is still undecided (Volm et al, 1991;Holzmayer et al, 1992;Segawa et al, 1993;Tabata et al, 1993;Abe et al, 1994;Oberli-Schrammli et al, 1994;Peoch et al, 1994;Thomas et al, 1994;Ota et al, 1995;Sugarawa et al, 1995;Beer et al, 1996;Chuman et al, 1996;Giaccone et al, 1996;Narasaki et al, 1996;Nooter et al, 1996;Stammler et al, 1996). In the present study, their incidence was equal in untreated SCLC and NSCLC (Tables 1 and 2), indicating that these drug efflux pumps are not themselves responsible for the very different sensitivities to etoposide in these two diseases.…”

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

“…Increased level of MRP1 expression has been found in a wide range of hematological and solid tumors (for references, see Table 3). Some of them, such as nonsmall-cell lung cancer (NSCLC) [13,109,150,175] or chronic lymphoblastic leukemia [63,111], generally exhibit high level of MRP1 expression and these tumors are intrinsically multidrug resistant, whereas others such as small-cell lung cancer (SCLC) [175], gastric carcinoma [2,34], neuroblastoma [114], and retinoblastoma [21] exhibit high MRP1 expression with a lower frequency. A correlation between the MRP1 expression and the stage of the tumor has been reported in certain tumor types, such as acute myeloblastic leukemia (AML) [165], myelodysplastic syndromes (MDS) [124], and prostate cancer [153].…”

“…On the other hand, in lung adenocarcinomas, a reverse correlation was seen with tumor grading [13]. High MRP1 expression was also found to be associated with higher grade of tumor differentiation in digestive tract carcinomas [160], endometrial carcinomas [72], and various subtypes of NSCLC, such as lung adenocarcinoma and squamous cell carcinoma [109,150].…”