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Immunohistochemical study of P-glycoprotein distribution in lung cancer
J L Pujol1, J Simony, V Gautier
1Centre Hospitalier Universitaire, Hôpital Arnaud de Villeneuve, Montpellier, France.
Insights
P-glycoprotein, encoded by the multidrug resistance (MDR1) gene, is frequently expressed in lung tumors. This expression does not significantly correlate with tumor stage, type, or ploidy, suggesting limited impact on chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- P-glycoprotein, encoded by the multidrug resistance (MDR1) gene, is implicated in multidrug resistance.
- Understanding P-glycoprotein expression in lung cancer is crucial for predicting treatment response.
Purpose of the Study:
- To investigate the expression of P-glycoprotein using the C219 antibody in primary lung tumors.
- To correlate P-glycoprotein expression with lung cancer subtypes, stage, ploidy, and neural cell adhesion molecule (NCAM) expression.
Main Methods:
- Indirect immunoperoxidase staining with the C219 monoclonal antibody was performed on 40 primary lung tumors.
- Tumor ploidy was analyzed using static cytometry.
- Expression of cluster 1 lung cancer antigens (S-L 11.14 and MOC-1) was assessed to identify NCAM-positive tumors.
Main Results:
- 45% of lung tumors showed strong P-glycoprotein expression, 20% showed weak expression, and 35% showed no reactivity.
- P-glycoprotein expression did not differ significantly between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
- No significant correlation was found between P-glycoprotein expression and tumor stage, NCAM expression, or ploidy status.
Conclusions:
- The internal epitope of MDR1-encoded P-glycoprotein is frequently expressed in various lung tumor types.
- P-glycoprotein expression in lung cancer appears independent of stage, histological type, and ploidy.
- The C219-detected epitope has a limited role in the reduced chemosensitivity observed in advanced or NSCLC cases.
Abstract:
Indirect immunoperoxidase was used to determine the reactivity of C219 (P-glycoCHEK C219, Centocor Diagnostics, Malvern, PA), a monoclonal antibody (Mab) with high affinity for an internal epitope of the P-glycoprotein encoded by the multidrug resistance (MDR1) gene, in 40 surgically resected primary lung tumours. C219 reactivity was qualitatively classified in seven small cell lung cancers (SCLC), 29 non small cell lung cancers (NSCLC), and four carcinoid tumours. Ploidy was analysed by means of static cytometry using a computer-assisted image processor following Feulgen staining of cytologic prints of 32/40 lung tumours. Indirect immunoperoxidase reactivities of Mabs S-L 11.14 and MOC-1 were also studied to characterize the expression of cluster 1 lung cancer antigens and hence to determine among the NSCLC those which expressed the neural cell adhesion molecule (NCAM). Eighteen (45%) lung tumours strongly expressed P-glycoprotein as an immunostaining of many islets of malignant cells or almost all malignant cells. In addition, 8/40 tumours (20%) showed a weak reactivity (few immunostained cells) and 14/40 (35%) no reactivity. There was no difference of reactivity when NSCLC were compared with SCLC. The expression of P-glycoprotein in NSCLC did not vary significantly when the stage of disease was considered. Among the 29 NSCLC, 10 (36%) expressed S-L 11.14 and MOC-1. The NCAM positive NSCLC did not show any difference of P-glycoprotein expression in comparison with NCAM negative ones. Finally, C219 immunoperoxidase reactivity did not significantly differ according to the ploidy status. In conclusion, the internal epitope of the P-glycoprotein encoded by the MDR1 gene is frequently expressed by lung tumours of any histological type. This expression is not higher in Stage III and IV lung cancers in comparison with Stage I and II ones, or in NSCLC in comparison with SCLC either. Thus, the C219 related epitope seems to have a weak implication in the lower chemosensitivity of both advanced stages and NSCLC.