title: Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens.
abstract: BACKGROUND
  The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors.
  
  
  METHODS
  In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells.
  
  
  RESULTS
  Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%.
  
  
  CONCLUSIONS
  The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 35249-6823, USA. dchhieng@path.uab.edu
authors.forename: D C
authors.initials: DC
authors.lastname: Chhieng
authors.forename: J F
authors.initials: JF
authors.lastname: Cangiarella
authors.forename: M F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: S
authors.initials: S
authors.lastname: Goswami
authors.forename: J M
authors.initials: JM
authors.lastname: Cohen
authors.forename: H T
authors.initials: HT
authors.lastname: Yee
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018287:Carcinoma, Large Cell / Q000276:immunology / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D007381:Intermediate Filament Proteins / Q000032:analysis; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology*; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000032:analysis; D011237:Predictive Value of Tests; D011663:Pulmonary Surfactants / Q000032:analysis / Q000276:immunology; D012680:Sensitivity and Specificity; D013961:Thyroid Gland; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D011663:Pulmonary Surfactants; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D007633:Keratins