Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1–q22.2 and losses of 17p13.3 and 11q23–q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers

Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck

<p>Abstract</p> <p>Background</p> <p>The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24–35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers.</p> <p>The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status.</p> <p>Methods</p> <p>Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry.</p> <p>Results</p> <p>Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake.</p> <p>Conclusion</p> <p>In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.</p

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours

Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV − tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1–0.6). A subpopulation of tumours (n=69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be amplified at 11q13 (OR=6.5, 95% CI=1.8–23.9). As HPV+ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway

MicroRNA profiling of cisplatinresistant oral squamous cell carcinoma cell lines enriched withcancer-stem-cell-like and epithelial-mesenchymal transition-type features

Oral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised. The resistant cells exhibited enhanced proliferative, clonogenic capacity with significant up-regulation of P-glycoprotein (ABCB1), c-Myc, survivin, β-catenin and a putative cancer-stem-like signature with increased expression of CD44, whereas the loss of E-cadherin signifies induced EMT phenotype. A comparative analysis of miRNA expression profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets (deregulated miRNAs in head and neck cancer) revealed resistance specific signature. Moreover, we observed similar expression pattern for these resistance specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent tumours compared to those with newly diagnosed primary tumours in patients with OSCC. All these results revealed that these miRNAs play an important role in the development of cisplatin-resistance mainly through modulating cancer stem-cell-like and EMT-type properties in OSCC

Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies.</p> <p>Methods</p> <p>Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest.</p> <p>Results</p> <p>Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; <it>KRAS </it>mutation; <it>TP53 </it>mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in <it>TP53 </it>in adenocarcinoma. A prognostic signature for disease recurrence, reflecting <it>KRAS </it>pathway activation, was validated in an independent test set.</p> <p>Conclusions</p> <p>These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.</p

Identification of TRPC6 as a possible candidate target gene within an amplicon at 11q21-q22.2 for migratory capacity in head and neck squamous cell carcinomas

Abstract: Background: Cytogenetic and gene expression analyses in head and neck squamous cell carcinomas (HNSCC) have allowed identification of genomic aberrations that may contribute to cancer pathophysiology. Nevertheless, the molecular consequences of numerous genetic alterations still remain unclear. Methods: To identify novel genes implicated in HNSCC pathogenesis, we analyzed the genomic alterations present in five HNSCC-derived cell lines by array CGH, and compared high level focal gene amplifications with gene expression levels to identify genes whose expression is directly impacted by these genetic events. Next, we knocked down TRPC6, one of the most highly amplified and over-expressed genes, to characterize the biological roles of TRPC6 in carcinogenesis. Finally, real time PCR was performed to determine TRPC6 gene dosage and mRNA levels in normal mucosa and human HNSCC tissues. Results: The data showed that the HNSCC-derived cell lines carry most of the recurrent genomic abnormalities previously described in primary tumors. High-level genomic amplifications were found at four chromosomal sites (11q21-q22.2, 18p11.31-p11.21, 19p13.2-p13.13, and 21q11) with associated gene expression changes in selective candidate genes suggesting that they may play an important role in the malignant behavior of HNSCC. One of the most dramatic alterations of gene transcription involved the TRPC6 gene (located at 11q21-q22.2) which has been recently implicated in tumour invasiveness. siRNA-induced knockdown of TRPC6 expression in HNSCC-derived cells dramatically inhibited HNSCC-cell invasion but did not significantly alter cell proliferation. Importantly, amplification and concomitant overexpression of TRPC6 was also found in HNSCC tumour samples. Conclusions: Altogether, these data show that TRPC6 is likely to be a target for 11q21-22.2 amplification that confers enhanced invasive behavior to HNSCC cells. Therefore, TRPC6 may be a promising therapeutic target in the treatment of HNSCC.This work was supported by Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria [FIS PI11/929 to M.-D.C and C. S.]; Red Tematica de Investigacion Cooperativa en Cancer [RD12/0036/0015] Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF); and Obra Social CajAstur-Instituto Universitario de Oncologia del Principado de Asturias.Bernaldo De Quirós, S.; Merlo, A.; Secades, P.; Zambrano, I.; Saenz De Santa María, I.; Ugidos, N.; Jantus Lewintre, E.... (2013). Identification of TRPC6 as a possible candidate target gene within an amplicon at 11q21-q22.2 for migratory capacity in head and neck squamous cell carcinomas. BMC Cancer. 13(116):1-9. https://doi.org/10.1186/1471-2407-13-116S1913116Akervall J: Genomic screening of head and neck cancer and its implications for therapy planning. Eur Arch Otorhinolaryngol. 2006, 263: 297-304. 10.1007/s00405-006-1039-1.Squire JA, Bayani J, Luk C, Unwin L, Tokunaga J, MacMillan C, Irish J, Brown D, Gullane P, Kamel-Reid S: Molecular cytogenetic analysis of head and neck squamous cell carcinoma: by comparative genomic hybridization, spectral karyotyping, and expression array analysis. Head Neck. 2002, 24: 874-887. 10.1002/hed.10122.Perez-Ordonez B, Beauchemin M, Jordan RC: Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol. 2006, 59: 445-453. 10.1136/jcp.2003.007641.Tan KD, Zhu Y, Tan HK, Rajasegaran V, Aggarwal A, Wu J, Wu HY, Hwang J, Lim DT, Soo KC, Tan P: Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma. Genes Chromosomes Cancer. 2008, 47: 353-362. 10.1002/gcc.20539.Rodrigo JP, Garcia LA, Ramos S, Lazo PS, Suarez C: EMS1 Gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res. 2000, 6: 3177-3182.Callender T, el-Naggar AK, Lee MS, Frankenthaler R, Luna MA, Batsakis JG: PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer. 1994, 74: 152-158. 10.1002/1097-0142(19940701)74:13.0.CO;2-K.Huang X, Gollin SM, Raja S, Godfrey TE: High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci U S A. 2002, 99: 11369-11374. 10.1073/pnas.172285799.Gorogh T, Weise JB, Holtmeier C, Rudolph P, Hedderich J, Gottschlich S, Hoffmann M, Ambrosch P, Csiszar K: Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma. J Pathol. 2007, 212: 74-82. 10.1002/path.2137.Begum A, Imoto I, Kozaki K, Tsuda H, Suzuki E, Amagasa T, Inazawa J: Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 In oral squamous-cell carcinoma. Cancer Sci. 2009, 100: 1908-1916. 10.1111/j.1349-7006.2009.01252.x.Secades P, Rodrigo JP, Hermsen M, Alvarez C, Suarez C, Chiara MD: Increase in gene dosage is a mechanism of HIF-1alpha constitutive expression in head and neck squamous cell carcinomas. Genes Chromosomes Cancer. 2009, 48: 441-454. 10.1002/gcc.20652.Singh B, Gogineni SK, Sacks PG, Shaha AR, Shah JP, Stoffel A, Rao PH: Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification. Cancer Res. 2001, 61: 4506-4513.Baldwin C, Garnis C, Zhang L, Rosin MP, Lam WL: Multiple microalterations detected at high frequency in oral cancer. Cancer Res. 2005, 65: 7561-7567.Roman E, Meza-Zepeda LA, Kresse SH, Myklebost O, Vasstrand EN, Ibrahim SO: Chromosomal aberrations in head and neck squamous cell carcinomas in Norwegian and Sudanese populations by array comparative genomic hybridization. Oncol Rep. 2008, 20: 825-843.Weber RG, Sommer C, Albert FK, Kiessling M, Cremer T: Clinically distinct subgroups of glioblastoma multiforme studied by comparative genomic hybridization. Lab Invest. 1996, 74: 108-119.Knuutila S, Bjorkqvist AM, Autio K, Tarkkanen M, Wolf M, Monni O, Szymanska J, Larramendy ML, Tapper J, Pere H: DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol. 1998, 152: 1107-1123.Menghi-Sartorio S, Mandahl N, Mertens F, Picci P, Knuutila S: DNA copy number amplifications in sarcomas with homogeneously staining regions and double minutes. Cytometry. 2001, 46: 79-84. 10.1002/cyto.1068.Imoto I, Tsuda H, Hirasawa A, Miura M, Sakamoto M, Hirohashi S, Inazawa J: Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy. Cancer Res. 2002, 62: 4860-4866.Dai Z, Zhu WG, Morrison CD, Brena RM, Smiraglia DJ, Raval A, Wu YZ, Rush LJ, Ross P, Molina JR: A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. Hum Mol Genet. 2003, 12: 791-801. 10.1093/hmg/ddg083.Bashyam MD, Bair R, Kim YH, Wang P, Hernandez-Boussard T, Karikari CA, Tibshirani R, Maitra A, Pollack JR: Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer. Neoplasia. 2005, 7: 556-562. 10.1593/neo.04586.Helias-Rodzewicz Z, Perot G, Chibon F, Ferreira C, Lagarde P, Terrier P, Coindre JM, Aurias A: YAP1 And VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas. Genes Chromosomes Cancer. 2010, 49: 1161-1171. 10.1002/gcc.20825.Fernandez LA, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM: YAP1 Is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates sonic hedgehog-driven neural precursor proliferation. Genes Dev. 2009, 23: 2729-2741. 10.1101/gad.1824509.Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T, Inazawa J: YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis. 2010, 32: 389-398.Chigurupati S, Venkataraman R, Barrera D, Naganathan A, Madan M, Paul L, Pattisapu JV, Kyriazis GA, Sugaya K, Bushnev S: Receptor channel TRPC6 is a key mediator of notch-driven glioblastoma growth and invasiveness. Cancer Res. 2010, 70: 418-427. 10.1158/0008-5472.CAN-09-2654.Ding X, He Z, Zhou K, Cheng J, Yao H, Lu D, Cai R, Jin Y, Dong B, Xu Y, Wang Y: Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst. 2010, 102: 1052-1068. 10.1093/jnci/djq217.Lansford CDGR, Bier H: Head and neck cancers. 1999, Dordrecht: Kluwer Academic Pressvan den Ijssel P, Tijssen M, Chin SF, Eijk P, Carvalho B, Hopmans E, Holstege H, Bangarusamy DK, Jonkers J, Meijer GA: Human and mouse oligonucleotide-based array CGH. Nucleic Acids Res. 2005, 33: e192-10.1093/nar/gni191.Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.Gollin SM: Chromosomal alterations in squamous cell carcinomas of the head and neck: window to the biology of disease. Head Neck. 2001, 23: 238-253. 10.1002/1097-0347(200103)23:33.0.CO;2-H.Smeets SJ, Braakhuis BJ, Abbas S, Snijders PJ, Ylstra B, van de Wiel MA, Meijer GA, Leemans CR, Brakenhoff RH: Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene. 2006, 25: 2558-2564. 10.1038/sj.onc.1209275.Snijders AM, Schmidt BL, Fridlyand J, Dekker N, Pinkel D, Jordan RC, Albertson DG: Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma. Oncogene. 2005, 24: 4232-4242. 10.1038/sj.onc.1208601.Canel M, Secades P, Garzon-Arango M, Allonca E, Suarez C, Serrels A, Frame M, Brunton V, Chiara MD: Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression. Br J Cancer. 2008, 98: 1274-1284. 10.1038/sj.bjc.6604286.Canel M, Secades P, Rodrigo JP, Cabanillas R, Herrero A, Suarez C, Chiara MD: Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number. Clin Cancer Res. 2006, 12: 3272-3279. 10.1158/1078-0432.CCR-05-1583.Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016/j.ccr.2006.10.008.Jarvinen AK, Autio R, Kilpinen S, Saarela M, Leivo I, Grenman R, Makitie AA, Monni O: High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx. Genes Chromosomes Cancer. 2008, 47: 500-509. 10.1002/gcc.20551.Lockwood WW, Chari R, Coe BP, Girard L, Macaulay C, Lam S, Gazdar AF, Minna JD, Lam WL: DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers. Oncogene. 2008, 27: 4615-4624. 10.1038/onc.2008.98.Weber A, Hengge UR, Stricker I, Tischoff I, Markwart A, Anhalt K, Dietz A, Wittekind C, Tannapfel A: Protein microarrays for the detection of biomarkers in head and neck squamous cell carcinomas. Hum Pathol. 2007, 38: 228-238. 10.1016/j.humpath.2006.07.012.Pacheco MM, Kowalski LP, Nishimoto IN, Brentani MM: Differential expression of c-jun and c-fos mRNAs in squamous cell carcinoma of the head and neck: associations with uPA, gelatinase B, and matrilysin mRNAs. Head Neck. 2002, 24: 24-32. 10.1002/hed.10009.Xie M, Sun Y, Li Y: Expression of matrix metalloproteinases in supraglottic carcinoma and its clinical implication for estimating lymph node metastases. Laryngoscope. 2004, 114: 2243-2248. 10.1097/01.mlg.0000149467.18822.59.Werner JA, Rathcke IO, Mandic R: The role of matrix metalloproteinases in squamous cell carcinomas of the head and neck. Clin Exp Metastasis. 2002, 19: 275-282. 10.1023/A:1015531319087.Zhang L, Ye DX, Pan HY, Wei KJ, Wang LZ, Wang XD, Shen GF, Zhang ZY: Yes-associated protein promotes cell proliferation by activating Fos related activator-1 in oral squamous cell carcinoma. Oral Oncol. 2011, 47: 693-697. 10.1016/j.oraloncology.2011.06.003.Yokoyama T, Osada H, Murakami H, Tatematsu Y, Taniguchi T, Kondo Y, Yatabe Y, Hasegawa Y, Shimokata K, Horio Y: YAP1 Is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation. Carcinogenesis. 2008, 29: 2139-2146. 10.1093/carcin/bgn200.Diep CH, Zucker KM, Hostetter G, Watanabe A, Hu C, Munoz RM, Von Hoff DD, Han H: Down-regulation of Yes associated protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. PLoS One. 7: e32783-Kang W, Tong JH, Chan AW, Lee TL, Lung RW, Leung PP, So KK, Wu K, Fan D, Yu J: Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Clin Cancer Res. 2011, 17: 2130-2139. 10.1158/1078-0432.CCR-10-2467.Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS, Haber DA: Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci U S A. 2006, 103: 12405-12410. 10.1073/pnas.0605579103.Guilbert A, Dhennin-Duthille I, Hiani YE, Haren N, Khorsi H, Sevestre H, Ahidouch A, Ouadid-Ahidouch H: Expression of TRPC6 channels in human epithelial breast cancer cells. BMC Cancer. 2008, 8: 125-10.1186/1471-2407-8-125.Yue D, Wang Y, Xiao JY, Wang P, Ren CS: Expression of TRPC6 in benign and malignant human prostate tissues. Asian J Androl. 2009, 11: 541-547. 10.1038/aja.2009.53.Cai R, Ding X, Zhou K, Shi Y, Ge R, Ren G, Jin Y, Wang Y: Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells. Int J Cancer. 2009, 125: 2281-2287. 10.1002/ijc.24551.Shi Y, Ding X, He ZH, Zhou KC, Wang Q, Wang YZ: Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer. Gut. 2009, 58: 1443-1450. 10.1136/gut.2009.181735.Thebault S, Flourakis M, Vanoverberghe K, Vandermoere F, Roudbaraki M, Lehen’kyi V, Slomianny C, Beck B, Mariot P, Bonnal JL: Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells. Cancer Res. 2006, 66: 2038-2047. 10.1158/0008-5472.CAN-05-0376.El Boustany C, Bidaux G, Enfissi A, Delcourt P, Prevarskaya N, Capiod T: Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation. Hepatology. 2008, 47: 2068-2077. 10.1002/hep.22263

Current potential and limitations of molecular diagnostic methods in head and neck cancer

Item does not contain fulltextTraditional diagnostic methods such as clinical assessment, histopathological examination and imaging techniques are limited in their capacity to provide information on prognosis and treatment choice of head and neck cancer. In recent years, molecular techniques have been developed that enabled us to get more insight into the molecular biological cellular pathways underlying tumor progression and metastasis. Correlation of these molecular changes with clinical events has been explored. However, consistently useful markers have not been identified yet, although many promising developments are in progress. It may be expected that in the near future, molecular markers will be useful for clinical purposes. In this paper, an overview will be given of the several molecular techniques that may have potential to be introduced in clinical practice in the management of head and neck squamous cell carcinoma.1 juni 201