title: Immunohistochemical study of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma of the lung.
abstract: OBJECTIVE
  In 1999, the World Health Organization categorized pulmonary large cell neuroendocrine carcinoma as a variant of large cell carcinoma. However, an optimal treatment for large cell neuroendocrine carcinoma has not been established yet. Recently, multimodality therapy combining both surgery and adjuvant chemotherapy has been reported as a useful treatment for large cell neuroendocrine carcinoma, but the effect of chemotherapy on it has not yet been fully investigated. Thus, we evaluated immunohistochemical data of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma.
  
  
  METHODS
  We identified 10 large cell neuroendocrine carcinomas (1.2%) out of 850 primary lung cancers that had been surgically resected. We examined the immunohistochemical staining of three drug-resistant proteins, namely, P-glycoprotein, metallothionein and glutathione S-transferase-pi to compare large cell neuroendocrine carcinoma with other histological types of lung cancer.
  
  
  RESULTS
  The mean tumor cell positivity rates for P-glycoprotein, metallothionein and glutathione S-transferase-pi in large cell neuroendocrine carcinoma were 0%, 2.4 +/- 3.6% and 35.0 +/- 37.5%, respectively. The positivity rates for P-glycoprotein and glutathione S-transferase-pi were significantly lower than those in adenocarcinoma (P = 0.0003, P = 0.0009). The positivity rate for glutathione S-transferase-pi was also lower than that in squamous cell carcinoma (P = 0.0387). These drug-resistant proteins showed similar expression pattern in both large cell neuroendocrine carcinoma and small cell carcinoma except glutathione S-transferase-pi.
  
  
  CONCLUSIONS
  Immunohistochemical expression of drug-resistant proteins in large cell neuroendocrine carcinoma was lower than that in adenocarcinoma and squamous cell carcinoma, and differences exist in drug-resistance between large cell neuroendocrine carcinoma and small cell carcinoma.
authors.affiliation: Department of Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okada
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018278:Carcinoma, Neuroendocrine / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D007564:Japan; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D013514:Surgical Procedures, Operative
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007527:Isoenzymes; D008668:Metallothionein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase