title: Intratumour variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer.
abstract: BACKGROUND
  Prognostic and predictive biomarkers are increasingly used to customise the treatment of patients with solid tumours. Intra- and inter-tumour heterogeneous distribution of biomarker expression is a potential confounder for the use of biomarkers, as small biopsies may not necessarily truly reflect the pattern of biomarker expression. It may also be an important factor in chemo resistance, as tumours with heterogeneous biomarker expression may potentially harbour chemo resistant tumour clones.
  
  
  METHODS
  Immunohistochemical evaluation of the expression of excision repair cross complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), class III-β-tubulin (TUBB-3), thymidylate synthase (TS), Ki-67 and ribonucleotide reductase M1 (RRM1) was performed in 15 separate areas in each of six small microscopically completely resected adenocarcinomas of the lung in order to elucidate any heterogeneous distribution.
  
  
  RESULTS
  Clinically relevant biomarker heterogeneity with respect to the expression of EGFR, ERCC1, RRM1, TUBB-3 and Ki-67 was observed in four (66%), four (66%), one (16%), three (50%) and five (83%) out of six tumours, respectively. Thus, heterogeneity could potentially allocate these tumours erroneously into high or low expressers by chance alone, according to previously reported cut-off values. In contrast, TS was almost completely homogenously distributed.
  
  
  CONCLUSIONS
  Most biomarkers examined, except for TS, showed clinically significant intratumour heterogeneity in 33-87% of tumours examined. This heterogeneity may influence results in studies investigating the therapeutic impact of predictive biomarkers in non-small cell lung cancer (NSCLC).
authors: Department of Oncology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: jan.nyrop.jakobsen@rh.regionh.dk.
authors: Jan Nyrop
authors: JN
authors: Jakobsen
authors: Department of Pathology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Eric
authors: E
authors: Santoni-Rugiu
authors: Department of Thoracic Surgery, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Jesper
authors: J
authors: Ravn
authors: Department of Oncology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Jens Benn
authors: JB
authors: Sørensen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors