title: Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers.
abstract: Chemoresistance is a major problem in the chemotherapy of non-small cell lung cancers (NSCLCs). Several mechanisms are thought to be involved in drug resistance, including those associated with apoptosis, drug transport and detoxification. Here, we investigated the predictive value of P53, Bcl-2 and lung resistance-related protein (LRP) expression for response to platinum-based chemotherapy, using transbronchial biopsy (TBB) specimens from patients with NSCLC. We evaluated TBB specimens from 57 patients with NSCLC who had not previously been treated with either chemotherapy or radiotherapy before TBB, and who were treated with systemic platinum-based chemotherapy. The specimens included 33 adenocarcinomas, 22 squamous cell carcinomas and two large cell carcinomas. One to 6 courses of chemotherapy were administered. Expression of P53, Bcl-2 and LRP was analyzed by immunohistochemistry using TBB specimens. Positive expression of P53, Bcl-2 and LRP was observed in 28 (49%), 41 (71%) and 42 (73%) of the 57 NSCLCs, respectively. P53 expression correlated significantly with response to chemotherapy in nonsquamous cell carcinomas, including adenocarcinomas and large cell carcinomas (response rates, 38% and 6% for patients with P53-positive and P53-negative tumors, respectively, P = 0.03). LRP expression significantly correlated inversely with response to chemotherapy in squamous cell carcinomas (response rates, 33% and 100% for patients with LRP-positive and LRP-negative tumors, respectively, P = 0.02). Bcl-2 expression did not correlate with response to chemotherapy. These findings indicate that immunostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ogura
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Katsushige
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein