Phenotype–genotype correlation: Challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses
Milo Frattini PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Milo Frattini and Federica Perrone contributed equally to this work.
Search for more papers by this authorFederica Perrone PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Milo Frattini and Federica Perrone contributed equally to this work.
Search for more papers by this authorSimona Suardi PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorDebora Balestra PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorStefano Caramuta PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorFederica Colombo PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorLisa Licitra MD
Department of Head and Neck, Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Search for more papers by this authorGiulio Cantù MD
Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Search for more papers by this authorMarco A. Pierotti PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Federazione Italiana Ricerca Cancro Institute of Molecular Oncology, Milan, Italy
Marco A. Pierotti and Silvana Pilotti are co-senior authors.
Search for more papers by this authorCorresponding Author
Silvana Pilotti MD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Marco A. Pierotti and Silvana Pilotti are co-senior authors.
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. ItalySearch for more papers by this authorMilo Frattini PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Milo Frattini and Federica Perrone contributed equally to this work.
Search for more papers by this authorFederica Perrone PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Milo Frattini and Federica Perrone contributed equally to this work.
Search for more papers by this authorSimona Suardi PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorDebora Balestra PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorStefano Caramuta PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorFederica Colombo PhD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Search for more papers by this authorLisa Licitra MD
Department of Head and Neck, Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Search for more papers by this authorGiulio Cantù MD
Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Search for more papers by this authorMarco A. Pierotti PhD
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Federazione Italiana Ricerca Cancro Institute of Molecular Oncology, Milan, Italy
Marco A. Pierotti and Silvana Pilotti are co-senior authors.
Search for more papers by this authorCorresponding Author
Silvana Pilotti MD
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. Italy
Marco A. Pierotti and Silvana Pilotti are co-senior authors.
Department of Pathology, Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano. ItalySearch for more papers by this authorAbstract
Background.
Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses shows microscopic features indistinguishable from colorectal cancer. Our aim was to verify whether the morphologic resemblances mirror genetic profile similarities.
Methods.
Twenty consecutive surgically treated ITAC cases, previously investigated for p16INK4a and TP53, were investigated for hMLH1, hMSH2, and β-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations.
Results.
One case was immunonegative for both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong β-catenin overexpression. No BRAF and APC truncating mutations were identified, whereas K-ras mutations were detected in 9 ITACs (50%).
Conclusions.
Our data confirm the phenotypic similarities at the genetic level between colorectal cancer and ITACs showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome 18q. By contrast, both frequency rate and type of inactivation of the APC-β-catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in the early development of ITAC (p16INK4a and TP53) and colorectal cancer (APC). © 2006 Wiley Periodicals, Inc. Head Neck, 2006
REFERENCES
- 1 Barnes L. Intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Am J Surg Pathol 1986; 10: 192–202.
- 2 Cathro HP, Mills SE. Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2. Am J Surg Pathol 2004; 28: 1026–1032.
- 3 Perrone F, Oggionni M, Birindelli S, et al. TP53, p14ARF, p16INK4a and H-ras gene molecular analysis in intestinal type adenocarcinoma of the nasal cavity and paranasal sinuses. Int J Cancer 2003; 105: 196–203.
- 4 Franchi A, Massi D, Baroni G, Santucci M. CDX-2 homeobox gene expression. Am J Surg Pathol 2003; 27: 1390–1391.
- 5 Franchi A, Massi D, Palomba A, Biancalani M, Santucci M. CDX-2, cytokeratin 7 and cytokeratin 20 immunohistochemical expression in the differential diagnosis of primary adenocarcinomas of the sinonasal tract. Virchows Arch 2004; 445: 63–67.
- 6 Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87: 159–170.
- 7 Houlston RS. What we could do now: molecular pathology of colorectal cancer. J Clin Pathol Mol Pathol 2001; 54: 206–214.
- 8 Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Volgestein B, Velculescu VE. RAF/RAS oncogenes and mismatch-repair status. Nature 2002; 418: 934.
- 9 Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759–767.
- 10 Ilyas M, Straub J, Tomlinson IP, Bodmer WF. Genetic pathways in colorectal and other cancers. Eur J Cancer 1999; 35: 1986–2002.
- 11 Frattini M, Balestra D, Suardi S, et al. Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res 2004; 10: 4015–4021.
- 12 Kennedy MT, Jordan RCK, Berean KW, Perez-Ordonez B. Expression pattern of CK7, CK20, CDX-2 and villin in intestinal-type sinonasal adenocarcinoma. J Clin Pathol 2004; 57: 932–937.
- 13 Perez-Ordonez B, Huynh NN, Berean KW, Jordan RC. Expression of mismatch repair proteins, beta catenin, and E cadherin in intestinal-type sinonasal adenocarcinoma. J Clin Pathol 2004; 57: 1080–1083.
- 14 Wu TT, Barnes L, Bakker A, Swalsky PA, Finkelstein S. K-ras-2 and p53 genotyping of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Mod Pathol 1996; 9: 199–204.
- 15 Saber AT, Nielsen LR, Dictor M, Hagmar L, Mikoczy Z, Wallin H. K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust. Cancer Lett 1998; 126: 59–65.
- 16
Pérez P,
Dominguez O,
González S,
González S,
Triviño A,
Suárez C.
ras gene mutations in ethmoid sinus adenocarcinoma.
Cancer
1999;
86:
255–264.
10.1002/(SICI)1097-0142(19990715)86:2<255::AID-CNCR9>3.0.CO;2-Z CAS PubMed Web of Science® Google Scholar
- 17 Rodrigues NR, Rowan A, Smith ME, et al. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A 1990; 87: 7555–7559.
- 18
Tang R,
Pei-Feng W,
Wang HC,
Wang JY,
Hsieh LL.
Mutations of p53 gene in human colorectal cancer: distinct frame-shifts among populations.
Int J Cancer
2001;
91:
863–868.
10.1002/1097-0215(200002)9999:9999<::AID-IJC1124>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 19 Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989; 244: 217–221.
- 20 Baker SJ, Preisinger AC, Jessup JM, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 1990; 50: 7717–7721.
- 21 Guan RJ, Fu Y, Holt PR, Pardee AB. Association of K-ras mutation with p16 methylation in human colon cancer. Gastroenterology 1999; 116: 1063–1071.
- 22 Yuen ST, Davies H, Chan TL, et al. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 2002; 62: 6451–6455.
- 23 Bearzatto A, Conte D, Frattini M, et al. p16INK4a hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer. Clin Cancer Res 2002; 8: 3782–3787.
- 24 Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949–954.
- 25 Frattini M, Ferrario C, Bressan P, et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene 2004; 23: 7436–7440.
- 26 Polakis P. Wnt signaling and cancer. Genes Dev 2000; 14: 1837–1851.
- 27 Licitra L, Suardi S, Bossi P, et al. Prediction of TP53 status for primary PFL chemotherapy in ethmoid sinus intestinal-type adenocarcinoma. J Clin Oncol 2004; 22: 4901–4906.
Citing Literature
