Immunohistochemical study of glutathione-related enzymes and proliferative antigens in lung cancer. Relation to cisplatin sensitivity.
BACKGROUND
With resected tumor tissue from 84 patients with lung cancer, the expression of glutathione peroxidase (GPX), glutathione reductase (GR), proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR) was examined in relation to cisdiamminedichloroplatinum (CDDP) sensitivity.


METHODS
The CDDP sensitivity was assessed from an increase of cells in the S-phase or G2M-phase by a DNA histogram after the tumor cells were incubated in a CDDP solution. The expression of GPX, GR, PCNA, and EGFR for each tumor was studied with an indirect immunoperoxidase technique on paraffin-embedded tissues.


RESULTS
The percentage of patients sensitive to CDDP according to the histologic type was 86% for small cell carcinomas, 40% for large cell carcinomas, 31% for squamous cell carcinomas, and 6% for adenocarcinomas. There was an inverse relationship between CDDP sensitivity and the frequency of GPX and GR expression, and both were significantly different among histologic types. The GPX and GR expression was significantly lower in the CDDP-sensitive group than in the resistant group (P < 0.01). However, the expression of PCNA and EGFR was significantly lower in the sensitive group in non-small cell carcinomas and squamous cell carcinomas (P < 0.05).


CONCLUSIONS
From the above findings, an immunohistochemical study of these antigens may be useful for predicting CDDP sensitivity in lung cancer.
Ogawa
J
J
First Department of Surgery, Tokai University School of Medicine, Isehara, Japan.
Iwazaki
M
M
Inoue
H
H
Koide
S
S
Shohtsu
A
A
D000951:Antigens, Neoplasm / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis*; D005980:Glutathione Reductase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology*; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen
D000951:Antigens, Neoplasm; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D066246:ErbB Receptors; D002945:Cisplatin