期刊论文详细信息
Diagnostic Pathology
A gene expression profile test to resolve head & neck squamous versus lung squamous cancers
Meredith Halks-Miller1  Ljubomir J Buturovic1  W David Henner1  Gregory J Kubicek2  Eloisa Fuentes1  Michael Walker1  Mira Marjanovic1  Rebecca Panos1  Anita Lal1 
[1] Pathwork Diagnostics, 595 Penobscot Dr, Redwood City, CA 94063, USA;Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15232, USA
关键词: neck cancer;    Head &;    Lung cancer;    Tissue of origin;    Gene expression;    Diagnostic test;   
Others  :  807374
DOI  :  10.1186/1746-1596-8-44
 received in 2013-01-11, accepted in 2013-02-28,  发布年份 2013
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【 摘 要 】

Background

The differential diagnosis between metastatic head & neck squamous cell carcinomas (HNSCC) and lung squamous cell carcinomas (lung SCC) is often unresolved because the histologic appearance of these two tumor types is similar. We have developed and validated a gene expression profile test (GEP-HN-LS) that distinguishes HNSCC and lung SCC in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160–gene classification model.

Methods

The test was validated in a blinded study using a pre-specified algorithm and microarray data files for 76 metastatic or poorly-differentiated primary tumors with a known HNSCC or lung SCC diagnosis.

Results

The study met the primary Bayesian statistical endpoint for acceptance. Measures of test performance include overall agreement with the known diagnosis of 82.9% (95% CI, 72.5% to 90.6%), an area under the ROC curve (AUC) of 0.91 and a diagnostics odds ratio (DOR) of 23.6. HNSCC (N = 38) gave an agreement with the known diagnosis of 81.6% and lung SCC (N = 38) gave an agreement of 84.2%. Reproducibility in test results between three laboratories had a concordance of 91.7%.

Conclusion

GEP-HN-LS can aid in resolving the important differential diagnosis between HNSCC and lung SCC tumors.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1753227817890930 webcite

【 授权许可】

   
2013 Lal et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Suo Z, Holm R, Nesland JM: Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours. Histopathology 1993, 23:45-54.
  • [2]Kaufmann O, Fietze E, Mengs J, Dietel M: Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 2001, 116:823-830.
  • [3]Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, Neville B, Richardson MS, Rosenzweig S, Sharma AK, Smith MM, Stewart S, Stuart RK: Oral cancer treatment. Curr Treat Options Oncol 2003, 4:27-41.
  • [4]Keith RL, Miller YE: Lung cancer: genetics of risk and advances in chemoprevention. Curr Opin Pulm Med 2005, 11:265-271.
  • [5]Levi F, Randimbison L, Te VC, La Vecchia C: Second primary cancers in laryngeal cancer patients. Eur J Cancer 2003, 39:265-267.
  • [6]Leong PP, Rezai B, Koch WM, Reed A, Eisele D, Lee DJ, Sidransky D, Jen J, Westra WH: Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst 1998, 90:972-977.
  • [7]Geurts TW, Nederlof PM, van den Brekel MW, van't Veer LJ, de Jong D, Hart AA, van Zandwijk N, Klomp H, Balm AJ, van Velthuysen ML: Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: metastasis or second primary? Clin Cancer Res 2005, 11:6608-6614.
  • [8]Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R: Platinum based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008, 359:1116-1127.
  • [9]Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H: Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010, 303:1070-1076.
  • [10]Groth SS, Maddaus MA: Open lobectomy for patients with stage I non-small cell lung cancer. Thorac Surg Clin 2007, 17:203-215.
  • [11]Landreneau RJ, Sugarbaker DJ, Mack MJ, Hazelrigg SR, Luketich JD, Fetterman L, Liptay MJ, Bartley S, Boley TM, Keenan RJ, Person PF, Weyant RJ, Naunheim KS: Wedge resection versus lobectomy for stage I (T1 N0 M0) non-small-cell lung cancer. J Thorac Cardiovasc Surg 1997, 113:691-698.
  • [12]Chudova D, Wilde JI, Wang ET, Wang H, Rabbee N, Egidio CM, Reynolds J, Tom E, Pagan M, Ted Rigl C, Friedman L, Wang CC, Lanman RB, Zeiger M, Kebebew E, Rosai J, Fellegara G, Livolsi VA, Kennedy GC: Molecular Classification of Thyroid Nodules Using High-Dimensionality Genomic Data. J Clin Endocrinol Metab 2010, 95:5296-5304.
  • [13]Pillai R, Deeter R, Rigl CT, Nystrom JS, Miller MH, Buturovic L, Henner WD: Validation and reproducibility of a microarray-based gene expression test for tumor identification in formalin-fixed, paraffin-embedded specimens. J Mol Diagn 2011, 13:48-56.
  • [14]Bloom G, Yang IV, Boulware D, Kwong KY, Coppola D, Eschrich S, Quackenbush J, Yeatman TJ: Multi-platform, multi-site, microarray-based human tumor classification. Am J Pathol 2004, 164:9-16.
  • [15]Tothill RW, Kowalczyk A, Rischin D, Bousioutas A, Haviv I, van Laar RK, Waring PM, Zalcberg J, Ward R, Biankin AV, Sutherland RL, Henshall SM, Fong K, Pollack JR, Bowtell DD, Holloway AJ: An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin. Cancer Res 2005, 65:4031-4040.
  • [16]Lal A, Panos R, Marjanovic M, Walker M, Fuentes E, Kapp DS, Henner DW, Buturovic LJ, Halks-Miller M: A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers. Oncotarget 2012, 3:212-223.
  • [17]Bammler T, Beyer RP, Bhattacharya S, Boorman GA, Boyles A, Bradford BU, Bumgarner RE, Bushel PR, Chaturvedi K, Choi D, Cunningham ML, Deng S, Dressman HK, Fannin RD, Farin FM, Freedman JH, Fry RC, Harper A, Humble MC, Hurban P, Kavanagh TJ, Kaufmann WK, Kerr KF, Jing L, Lapidus JA, Lasarev MR, Li J, Li YJ, Lobenhofer EK, Lu X: Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods 2005, 2:351-356.
  • [18]Dobbin KK, Beer DG, Meyerson M, Yeatman TJ, Gerald WL, Jacobson JW, Conley B, Buetow KH, Heiskanen M, Simon RM, Minna JD, Girard L, Misek DE, Taylor JM, Hanash S, Naoki K, Hayes DN, Ladd-Acosta C, Enkemann SA, Viale A, Giordano TJ: Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays. Clin Cancer Res 2005, 11:565-572.
  • [19]Irizarry RA, Warren D, Spencer F, Kim IF, Biswal S, Frank BC, Gabrielson E, Garcia JG, Geoghegan J, Germino G, Griffin C, Hilmer SC, Hoffman E, Jedlicka AE, Kawasaki E, Martinez-Murilla F, Morsberger L, Lee H, Peterson D, Quackenbush J, Scott A, Wilson M, Yang Y, Ye SQ, Yu W: Multiple-laboratory comparison of microarray platforms. Nat Methods 2005, 2:345-350.
  • [20]Dunn TA, Fedor H, Isaacs WB, De Marzo AM, Luo J: Genome-wide expression analysis of recently processed formalin-fixed paraffin embedded human prostate tissues. Prostate 2009, 69:214-218.
  • [21]Fedorowicz G, Guerrero S, Wu TD, Modrusan Z: Microarray analysis of RNA extracted from formalin-fixed, paraffin-embedded and matched fresh-frozen ovarian adenocarcinomas. BMC Med Genomics 2009, 2:23. BioMed Central Full Text
  • [22]Penland SK, Keku TO, Torrice C, He X, Krishnamurthy J, Hoadley KA, Woosley JU, Thomas NE, Perou CM, Sandler RS, Sharpless NE: RNA expression analysis of formalin-fixed paraffin-embedded tumors. Lab Invest 2007, 87:383-391.
  • [23]Chen C, Mendez E, Houck J, Fan W, Lohavanichbutr P, Doody D, Yueh B, Futran ND, Upton M, Farwell DG, Schwartz SM, Zhao LP: Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2008, 17:2152-2162.
  • [24]Ziober AF, Patel KR, Alawi F, Gimotty P, Weber RS, Feldman MM, Chalian AA, Weinstein GS, Hunt J, Ziober BL: Identification of a gene signature for rapid screening of oral squamous cell carcinoma. Clin Cancer Res 2006, 12:5960-5971.
  • [25]Gonzalez HE, Gujrati M, Frederick M, Henderson Y, Arumugam J, Spring PW, Mitsudo K, Kim HW, Clayman GL: Identification of 9 genes differentially expressed in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2003, 129:754-759.
  • [26]Pyeon D, Newton MA, Lambert PF, den Boon JA, Sengupta S, Marsit CJ, Woodworth CD, Connor JP, Haugen TH, Smith EM, Kelsey KT, Turek LP, Ahlquist P: Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers. Cancer Res 2007, 67:4605-4619.
  • [27]Talbot SG, Estilo C, Maghami E, Sarkaria IS, Pham DK, O'charoenrat P, Socci ND, Ngai I, Carlson D, Ghossein R, Viale A, Park BJ, Rusch VW, Singh B: Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung. Cancer Res 2005, 65:3063-3071.
  • [28]Kulkarni A, Pillai R, Ezekiel AM, Henner WD, Handorf CR: Comparison of histopathology to gene expression profiling for the diagnosis of metastatic cancer. Diagn Pathol 2012, 7:110. BioMed Central Full Text
  • [29]Varma S, Simon R: Bias in error estimation when using cross-validation for model selection. BMC Bioinformatics 2006, 7:91. BioMed Central Full Text
  • [30]Berry SM, Carlin BP, Lee J, Muller P: Bayesian adaptive methods for clinical trials. Boca Raton: CRC Press; 2010.
  • [31]Spiegelhalter DJ, Abrams KR, Myles JP: Bayesian approaches to clinical trials and health care evaluation. Chichester (UK): Wiley; 2004.
  • [32]Zweig MH, Campbell G: Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993, 39:561-577.
  • [33]Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM: The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 2003, 56:1129-1135.
  • [34]Cohen J: A coefficient of agreement for nominal scales. Educ Psychol Meas 1960, 20:37-46.
  • [35]Perez-Gil J: Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics. Pediatr Pathol Mol Med 2001, 20:445-469.
  • [36]Kingma PS, Whitsett JA: In defense of the lung: surfactant protein A and surfactant protein D. Curr Opin Pharmacol 2006, 6:277-283.
  • [37]Vaid M, Floros J: Surfactant protein DNA methylation: a new entrant in the field of lung cancer diagnostics? Oncol Rep 2009, 21:3-11.
  • [38]Lin Z, Thomas NJ, Bibikova M, Seifart C, Wang Y, Guo X, Wang G, Vollmer E, Goldmann T, Garcia EW, Zhou L, Fan JB, Floros J: DNA methylation markers of surfactant proteins in lung cancer. Int J Oncol 2007, 31:181-191.
  • [39]Srodon M, Westra WH: Immunohistochemical staining for thyroid transcription factor-1: a helpful aid in discerning primary site of tumor origin in patients with brain metastases. Hum Pathol 2002, 33:642-645.
  • [40]Rekhtman N, Ang DC, Sima CS, Travis WD, Moreira AL: Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol 2011, 24:1348-1359.
  • [41]Downey P, Cummins R, Moran M, Gulmann C: If it's not CK5/6 positive, TTF-1 negative it's not a squamous cell carcinoma of lung. Apmis 2008, 116:526-529.
  • [42]Fujita J, Ohtsuki Y, Bandoh S, Ueda Y, Kubo A, Tojo Y, Yamaji Y, Ishida T: Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines. Lung Cancer 2003, 39:31-36.
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