Cancer Research AM No Date
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Freier, K.
Right arrow Articles by Hofele, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Freier, K.
Right arrow Articles by Hofele, C.
[Cancer Research 63, 1179-1182, March 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Tissue Microarray Analysis Reveals Site-specific Prevalence of Oncogene Amplifications in Head and Neck Squamous Cell Carcinoma1

Kolja Freier, Stefan Joos, Christa Flechtenmacher, Frauke Devens, Axel Benner, Franz X. Bosch, Peter Lichter and Christof Hofele2

Deutsches Krebsforschungszentrum, Abteilung Molekulare Genetik (H0700) [K. F., S. J., F. D., P. L.]; and Deutsches Krebsforschungszentrum, Abteilung für Biostatistik [A. B.], Heidelberg D-69120, Germany, and Klinik für Mund-, Kiefer- und Gesichtschirurgie [K. F., C. H.], Pathologisches Institut [C. F.], and Molekularbiologisches Labor der Klinik für Hals-, Nasen-, Ohrenheilkunde [F. X. B.], Universitätsklinikum Heidelberg, D-69210 Heidelberg, Germany


   ABSTRACT
Top
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 REFERENCES
 
Fluorescence in situ hybridization was applied on a collection of 609 squamous cell carcinomas of the head and neck (HNSCCs),including 511 primary carcinomas of different clinical stage and anatomical localization and 98 recurrent carcinomas, second primary carcinomas, and regional metastases on a tissue microarray. The overall prevalence of amplifications of five oncogenes analyzed was 34.5% for CCND1, 12.7% for EGFR, 8.8% for MYC, 6.2% for ZNF217, and 3.6% for ERBB2. CCND1 amplifications were associated with the pharyngeal site in primary carcinomas (P < 0.001), whereas amplifications of ZNF217 were less frequent in pharyngeal carcinomas as compared with primary oral and laryngeal carcinomas (P = 0.02). The amplification pattern of these oncogenes suggests that different molecular pathways are involved in HNSCCs of different localizations.


   Introduction
Top
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 REFERENCES
 
HNSCC3 is characterized by local tumor aggressiveness, high rate of early recurrences, and development of second primary carcinomas. Despite modern therapeutic strategies like adjuvant and neoadjuvant radio- and chemotherapy additional to operational management of the tumor, the overall 5-year survival rate does not exceed 55% (1) . Furthermore, HNSCCs are a heterogeneous group presenting as tumors of different anatomical regions such as the oral cavity, the oro-/hypopharynx, and the larynx. These subentities show different, often contrary, biological and clinical behavior. For example, the potential of forming metastases is very low in laryngeal carcinoma, whereas it is quite common in pharyngeal carcinomas. It could be shown that the various HNSCC subentities exhibit different genetic alterations, which could explain the different biological behavior of the tumors (2) .

It is widely accepted that HNSCCs develop in a multistep pathway of genetic aberrations (3) . Among others, amplifications of several oncogenes were previously detected (4) . To determine the role of oncogene amplification for the clinical course of HNSCC, we applied the approach of TMA, a novel high-throughput technology that allows screening of tumor specimens on a large scale for molecular genetic alterations and changes in protein expression (5) . We generated a tissue array of more than 600 clinically well-defined HNSCCs and detected genomic amplification of proto-oncogenes CCND1, MYC, EGFR, ERBB2, and ZNF217 using FISH. A possible association of amplification of these oncogenes with stage, anatomical site, or long-term survival of the patients was assessed.


   Materials and Methods
Top
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 REFERENCES
 
HNSCCs.
Altogether 609 HNSCCs from 584 patients were analyzed in this study. Five hundred eleven of the tumors were untreated primary carcinomas; 98 of the tumors were scored as advanced disease tumors, i.e., recurrent tumors, second primary tumors, and regional metastases. The primary carcinomas were divided into three groups corresponding to their anatomical site (oral cavity, pharynx, larynx) and graded according to the Tumor-Node-Metastasis (TNM) system and the Unio Internationale Contra Cancrum (UICC) stage. Data about tumor localization and stage are summarized in Table 1Citation . Advanced-disease tumors were not subdivided according to their different localization and TNM grade. Formalin-fixed, paraffin-embedded tumor samples were obtained from the archives of the Institute of Pathology of the University of Heidelberg and several centers connected to it. For control experiments, uvula mucosa tissue from healthy donors was available. The evaluation of the clinical follow-up of the patients was performed using data from the Department of Oto-Rhino-Laryngology and of the Department of Oral and Maxillofacial Surgery of the University of Heidelberg. The approval for this study was given by the Medical Ethics Commission of the Universitätsklinikum Heidelberg.


View this table:
[in this window]
[in a new window]

  		Table 1 Number of amplifications for all of the analyzed oncogenes with respect to localization and stage

 
Generation of TMAs.
H&E-stained sections were made from each paraffin block to define representative tumor regions. From these regions, tissue cylinders with a diameter of 0.6 mm were obtained and arrayed into a recipient block using the tissue chip microarrayer (Beecher Instruments, Silver Spring, MD). The recipient block was subsequently cut into 5-µm sections on silanized glass slides that were treated with 3-aminopropylemethoxysilane before cutting to support adhesion of the tissue samples.

FISH Analysis.
Two-color FISH to the sections of the tissue microarray was performed using Spectrum Orange-labeled probes for CCND1, MYC, ERBB2, ZNF217, and EGFR and Spectrum Green-labeled centromeric probes of the chromosomes 7, 8, 11, and 17 (Vysis, Downers Grove, IL). Pretreatment of slides, hybridization, posthybridization processing, and signal detection were performed as described previously (6) . Tumor signals were scored as amplified with 10% of cells showing eight or more signals or tight clusters of signals of the oncogene probe. Less than eight signals per cell were considered as low-level gains and not scored as gene amplification. The signals of the centromeric probes were used to control adequate hybridization and to exclude artifacts.

Statistical Analysis.
Fisher’s exact test was used to compare the prevalence of gene amplification in primary carcinomas with that of advanced disease carcinomas. For primary carcinomas, the distributions of amplifications according to anatomical site, tumor classification, and stage were compared using Fisher’s exact test. An estimation was made about the distribution of amplifications in different localization and clinical stages. Every tumor site was analyzed individually, T1-T2 tumors were compared with T3-T4 tumors and stage I-III carcinomas with stage IV carcinomas. Estimation of the survival time distribution of patients with primary carcinomas was done using the method proposed by Kaplan and Meier. Survival curves were compared by log-rank tests. A result was considered as statistically significant if the corresponding Ps were <=0.05. The median follow-up time was 48.5 months.


   Results
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 REFERENCES
 
FISH analysis was performed on the HNSCC microarray with oncogenes CCND1, MYC, EGFR, ERBB2, and ZNF217 (Fig. 1)Citation . The number of gene amplifications according to the different subsets of tumors is summarized in Table 1Citation . There was no statistically significant difference between the samples of primary tumors and advanced disease tumors concerning the prevalence of individual oncogene amplification (CCND1, P = 0.15; MYC, P = 0.66; ERBB2, P = 0.33; EGFR, P = 0.19; ZNF217, P = 1.0). Regarding amplification of CCND1, a highly significant difference between the sites of the primary carcinomas was revealed. Prevalence of CCND1 amplification was significantly higher in pharyngeal tumors than in oral and laryngeal carcinomas (P < 0.001). ZNF217 amplifications were significantly less common in pharyngeal tumors than in tumors of the oral cavity and the larynx (P = 0.02; Fig. 2Citation ). With respect to the remaining oncogenes, there was no significant effect on the prevalence of amplification in different tumor sites. (MYC, P = 0.54; ERBB2, P = 0.64; EGFR, P = 0.41).



View larger version (105K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 1. Amplification of CCND1 (top) and ERBB2 (bottom) in primary HNSCCs.

 


View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 2. Frequency of CCND1 (P = 0.001) and ZNF217 (P = 0.02) amplification in different anatomic sites of primary HNSCC.

 
We further analyzed the impact of oncogene amplification on clinical stage and tumor localization in primary carcinoma. No association was found between the number of amplifications and any of the two groups of tumor classifications (CCND1, P = 0.24; MYC, P = 0.7; ERBB2, P = 0.4; EGFR, P = 0.16; ZNF217, P = 1.0). However, there were significantly more CCND1 amplifications in stage IV carcinomas than in the group of carcinomas in stage I-III (P < 0.001; Fig. 3Citation ). Because stage IV is more common in pharyngeal carcinomas (81.75% of all primary carcinomas with pharyngeal site) than in carcinomas of the oral cavity (62.8%) and the larynx (40%) in our collective, this effect can mainly be explained by the high prevalence of CCND1 amplifications in pharyngeal carcinomas. For the other four oncogenes, no statistically significant difference was detected between stage I-III and stage IV (MYC, P = 1.0; ERBB2, P = 1.0; EGFR, P = 0.41; ZNF217, P = 0.65).



View larger version (14K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 3. Frequency of CCND1 amplification in HNSCC of different tumor classifications (P = 0.24) and stages (P < 0.001). T 1/2, T1–2; T 3/4, T3–4; S I-III, stage I-III; S IV, stage IV.

 
An analysis of the survival curves revealed no association between the amplification of any of the five oncogene probes and overall survival (CCND1, P = 0.24; MYC, P = 0.71, ERBB2, P = 0.76; EGFR, P = 0.57; ZNF217, P = 0.78).


   Discussion
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
REFERENCES
 
The combination of TMA and FISH is a powerful approach to detecting gene amplification in large series of tumor specimens. In this study, the TMA technology was used to study a large series of HNSCCs. This allowed us to extend previous results (7 , 8) concerning the prevalence of oncogene amplification in HNSCC. Notably, our data showed that CCND1 amplifications were more common in pharyngeal carcinomas than in carcinomas of the larynx and of the oral cavity. This difference was highly significant and corresponds with elevated cyclin D1 protein expression levels that were observed previously in pharyngeal carcinomas (9) . Additionally, we observed a significantly higher number of amplifications in stage IV tumors than in stage I-III tumors. One might, therefore, speculate that CCND1 is directly involved in the formation of regional metastasis. However, the association between CCND1 amplification and metastasis can be explained as well by the higher frequency of CCND1 amplifications in tumors of the pharynx, for which other molecular changes could also lead to an increased risk for metastasis. Interestingly, the distribution of amplifications did not differ between small and large tumors (T1–2 versus T3–4), suggesting a specific role of CCND1 in the early carcinogenesis of HNSCC (Fig. 3)Citation . This is also supported by previous findings of CCND1 amplifications in preneoplastic oral lesions (10) . In conclusion, our data strongly indicate that CCND1 amplification is characteristic for pharyngeal HNSCC compared with carcinomas of the larynx and the oral cavity and, therefore, has the function of a site-specific molecular alteration.

The impact of CCND1 amplification on long-term prognosis is the subject of ongoing discussion (6 , 7) . No such correlation was found in our patient collective. On the basis of a CGH-analysis on 113 primary HNSCCs by Bockmühl et al. (11) , amplification of chromosomal subregion 11q13 was described as of prognostic relevance. It should be noted, however, that a relatively large number of parameters were analyzed in this study, and, therefore, the data obtained from this tumor collection might not be representative of the HNSCC entity as a whole. Alternatively, if the amplification of 11q13 is of prognostic relevance, CCND1 might not be the only relevant gene for HNSCC progression in this subregion, but, instead, other candidate genes should be taken into account. For example, EMS1 amplification has been found to predict for patients survival (8) . Other potential candidate genes found to be amplified on 11q13 in HNSCC include INT2, FGF4, and HST1 (12) . Certainly, the TMA presented in the present study will be highly valuable to further delineate the prognostic role of candidate genes located at 11q13 in HNSCC.

The epidermal growth factor ERBB2(HER2/NEU) has become a subject of interest in HNSCCs because the amplification of ERBB2(HER2/NEU) demonstrated its power to predict patient outcome in breast cancer (13) . Furthermore the ERBB2 gene product represents a target for specific therapy with a monoclonal antibody (Herceptin). In HNSCC, data about overall prevalence of ERBB2 amplifications are very rare. Recently, amplifications of ERBB2 were detected in four cases of oropharyngeal carcinomas for the first time (14) . On the protein level, ERBB2 overexpression has been observed in HNSCC, but its influence on survival rates remained open (15) . According to the present study, 4.2% of primary HNSCCs were found to be harboring amplification of ERBB2 without significant difference concerning tumor site and stage. Furthermore, there was no impact on patients’ survival. Although ERBB2 amplifications are generally infrequent in HNSCC and, therefore, unlikely to serve as potent clinical markers, these findings suggest that Herceptin therapy may be a therapeutic option in a small fraction of HNSCC. Concerning the oncogenes ERBB1 and MYC, no correlation with site, stage, or clinical outcome was assessed.

Copy number gains of chromosomal subregion 20q13 has been frequently found in CGH-studies of HNSCCs (11 , 16) . One of the candidate genes in this region is ZNF217, which is predicted to encode two alternately spliced, Krüppel-like transcription factors and has been shown to be amplified in breast cancer (17) . In this study, the overall prevalence of ZNF217 amplification was revealed for the first time in HNSCC, but no influence on the clinical follow-up was observed. This is in accordance with the finding that 20q13 is not considered as a critical region with prognostic significance in HNSCCs (11) . However, we detected a significantly lower rate of ZNF217 amplifications in pharyngeal as compared with oral and laryngeal carcinomas. This further indicates that HNSCCs of different anatomical sites are characterized by a different pattern of genetic aberrations and, therefore, might represent different subentities of this tumor type. Our data are supported by recent analyses that also revealed different genetic alteration patterns depending on the anatomical site in HNSCC (2 , 18 , 19) . In conclusion, we demonstrate that molecular alterations and their relevance in the etiology and progression of HNSCC can be efficiently assessed by combining FISH and TMA technology. We showed in a large collection of HNSCCs that different amplification patterns of two oncogenes, CCND1 and ZNF217, are found in HNSCC of different anatomical sites, which strongly suggests that different molecular pathways may be involved. This may contribute to a multistep pathway model of pathogenesis, eventually allowing individual clinical risk assessment and therapy decision in the future.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by the Deutsche Krebshilfe (No. 10-1745-Ho), by the Medizinische Fakultät der Universität Heidelberg (No. 325/2000), and by the National Genome Research Network, Germany (No. KB-P2T02) Back

2 To whom requests for reprints should be addressed, at Klinik für Mund-, Kiefer- und Gesichtschirurgie der Universität Heidelberg, Im Neuenheimer Feld 400, D-69210 Heidelberg, Germany. Phone: 49-6221-56-7327; Fax: 49-6221-56-33532; E-mail: Christof_Hofele{at}med.uni-heidelberg.de Back

3 The abbreviations used are: HNSCC, squamous cell carcinoma of the head and neck; TMA, tissue microarray analysis; FISH, fluorescence in situ hybridization; C64, comparative genomic hybridization. Back

Received 9/27/02. Accepted 1/27/03.


   REFERENCES
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
 REFERENCES
 

  1. Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics. CA Cancer J. Clin., 49: 8-31, 1999.[Abstract/Free Full Text]
  2. Poetsch M., Kleist B., Lorenz G., Herrman F. H. Different numerical chromosomal aberrations detected by FISH in oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma. Histopathology, 34: 234-240, 1999.[Medline]
  3. Califano J., van der Riet P., Westra W., Nawroz H., Clayman G., Piantadosi S., Corio R., Lee D., Greenberg B., Koch W., Sidransky D. Genetic progression model for head and neck cancer: implications for field cancerization.. Cancer Res., 56: 2488-2492, 1996.[Abstract/Free Full Text]
  4. Crowe D. L., Hacia J. G., Hsiek C. L., Sinha U. K., Rice H. Molecular pathology of head and neck cancer. Histol. Histopathol., 17: 909-914, 2002.[Medline]
  5. Kallioniemi O-P., Wagner U., Kononen J., Sauter G. Tissue microarray technology for high-throughput molecular profiling of cancer. Hum. Mol. Genet., 10: 657-662, 2001.[Abstract/Free Full Text]
  6. Bubendorf L., Kononen J., Koivisto P., Schraml P., Moch H., Gasser T. C., Willi n., Mihatsch M. J., Sauter G., Kallioniemi O-P. Survey of gene amplifications during prostate cancer progression by high-throughput fluorescence in situ hybridization on tissue microarrays. Cancer Res., 59: 803-806, 1999.[Abstract/Free Full Text]
  7. Kyomoto R., Kumazawa H., Toda Y., Sakaida N., Okamura A., Iwanage M., Shintaku M., Yamashita T., Hiai H., Fukumoto M. Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma. Int. J. Cancer, 74: 576-581, 1997.[Medline]
  8. Rodrigo J. P., Garcia L. A., Ramos S., Lazo P. S., Suárez C. EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin. Cancer Res., 6: 3177-3182, 2000.[Abstract/Free Full Text]
  9. Takes R. P., Baatenburg de Jong R. J., Schuuring E., Litvinov S. V., Hermans J., van Krieken J. H. J. M. Differences in expression of oncogenes and tumor suppressor genes in different sites of head and neck squamous cell carcinoma. Anticancer Res., 18: 4793-4800, 1998.[Medline]
  10. Rousseau A., Lim. M. S., Lin Z., Jordan R. C. K. Frequent cyclin D1 gene amplification and protein overexpression in oral epithelial dysplasias. Oral Oncol., 37: 268-275, 2001.[Medline]
  11. Bockmühl U., Schlüns K., Küchler I., Petersen S., Petersen I. Genetic imbalances with impact on survival in head and neck cancer patients. Am. J. Pathol., 157: 369-375, 2000.[Abstract/Free Full Text]
  12. Wang M. B., Alavi S., Engstrom M., Lee J., Namazie A., Motamed F., Srivatsan E. S. Detection of chromosome 11q13 amplification in head and neck cancer using fluorescence in situ hybridization. Anticancer Res., 19: 925-932, 1999.[Medline]
  13. Pauletti G., Dandekar S., Rong H., Ramos L., Peng H., Seshadri R., Slamon D. J. Assessments of methods for tissue-based detection of HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry.. J. Clin. Oncol., 18: 3651-3664, 2000.[Abstract/Free Full Text]
  14. Khan A. J., King B. L., Smith B. D., Smith G. L., DiGiovanna M. P., Carter D., Haffty B. G. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Clin. Cancer Res., 8: 540-548, 2002.[Abstract/Free Full Text]
  15. Ibrahim S. O., Vasstrand E. N., Liavaag P. G., Johannessen A. C., Lillehaug J. R. Expression of c-erbB proto-oncogene family members in squamous cell carcinoma of the head and neck. Anticancer Res., 17: 4539-4546, 1997.[Medline]
  16. Weber R. G., Scheer M., Born I. A., Joos S., Cobbers J. M. J., Hofele C., Reifenberger G., Zöller J. E., Lichter P. Recurrent chromosomal imbalances detected in biopsy material from oral premalignant and malignant lesions by combined tissue microdissection, universal DNA amplification and comparative genomic hybridization. Am. J. Pathol., 153: 295-303, 1998.[Abstract/Free Full Text]
  17. Collins C., Rommens J. M., Kowbel D., Godfrey T., Tanner M., Hwang S., Polikoff D., Nonet G., Cochran J., Myambo K., et al Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.. Proc. Natl. Acad. Sci. USA, 95: 8703-8708, 1998.[Abstract/Free Full Text]
  18. Steinhart H., Bohlender J., Iro H., Jung V., Constantinidis J., Gebhart E., Pahl S., Urbschat S. DNA amplification on chromosome 7q in squamous cell carcinoma of the tongue. Int. J. Oncol., 19: 851-855, 2001.[Medline]
  19. Huang Q., Yu G. P., McCormick S. A., Mo J., Datta B., Mahimkar M., Lazarus P., Schaffer A. A., Desper R., Schantz S. P. Genetic differences detected by comparative hybridization in head and neck squamous cell carcinoma from different tumor sites: construction of oncogenetic trees for tumor progression.. Genes Chromosomes Cancer, 34: 224-233, 2002.[Medline]



This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
T. L. Lee, X. P. Yang, B. Yan, J. Friedman, P. Duggal, L. Bagain, G. Dong, N. T. Yeh, J. Wang, J. Zhou, et al.
A Novel Nuclear Factor-{kappa}B Gene Signature Is Differentially Expressed in Head and Neck Squamous Cell Carcinomas in Association with TP53 Status
Clin. Cancer Res., October 1, 2007; 13(19): 5680 - 5691.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
D. Uchida, T. Onoue, Y. Tomizuka, N. M. Begum, Y. Miwa, H. Yoshida, and M. Sato
Involvement of an Autocrine Stromal Cell Derived Factor-1/CXCR4 System on the Distant Metastasis of Human Oral Squamous Cell Carcinoma
Mol. Cancer Res., July 1, 2007; 5(7): 685 - 694.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. A. Forastiere and B. A. Burtness
Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer--More Insights, but More Questions
J. Clin. Oncol., June 1, 2007; 25(16): 2152 - 2155.
[Full Text] [PDF]

Home page
 JCOHome page
S. Temam, H. Kawaguchi, A. K. El-Naggar, J. Jelinek, H. Tang, D. D. Liu, W. Lang, J.-P. Issa, J. J. Lee, and L. Mao
Epidermal Growth Factor Receptor Copy Number Alterations Correlate With Poor Clinical Outcome in Patients With Head and Neck Squamous Cancer
J. Clin. Oncol., June 1, 2007; 25(16): 2164 - 2170.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
E. E. Evans, A. D. Henn, A. Jonason, M. J. Paris, L. M. Schiffhauer, M. A. Borrello, E. S. Smith, D. M. Sahasrabudhe, and M. Zauderer
C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer.
Mol. Cancer Ther., November 1, 2006; 5(11): 2919 - 2930.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. H. Chung, K. Ely, L. McGavran, M. Varella-Garcia, J. Parker, N. Parker, C. Jarrett, J. Carter, B. A. Murphy, J. Netterville, et al.
Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas
J. Clin. Oncol., September 1, 2006; 24(25): 4170 - 4176.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Mendrzyk, A. Korshunov, A. Benner, G. Toedt, S. Pfister, B. Radlwimmer, and P. Lichter
Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma.
Clin. Cancer Res., April 1, 2006; 12(7): 2070 - 2079.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M.-H. Yang, W.-C. Chiang, T.-Y. Chou, S.-Y. Chang, P.-M. Chen, S.-C. Teng, and K.-J. Wu
Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation
Clin. Cancer Res., January 15, 2006; 12(2): 507 - 515.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Mathas, K. Johrens, S. Joos, A. Lietz, F. Hummel, M. Janz, F. Jundt, I. Anagnostopoulos, K. Bommert, P. Lichter, et al.
Elevated NF-{kappa}B p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas
Blood, December 15, 2005; 106(13): 4287 - 4293.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. Mendrzyk, B. Radlwimmer, S. Joos, F. Kokocinski, A. Benner, D. E. Stange, K. Neben, H. Fiegler, N. P. Carter, G. Reifenberger, et al.
Genomic and Protein Expression Profiling Identifies CDK6 As Novel Independent Prognostic Marker in Medulloblastoma
J. Clin. Oncol., December 1, 2005; 23(34): 8853 - 8862.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Z. Yu, P. M. Weinberger, B. G. Haffty, C. Sasaki, C. Zerillo, J. Joe, D. Kowalski, J. Dziura, R. L. Camp, D. L. Rimm, et al.
Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma
Clin. Cancer Res., February 1, 2005; 11(3): 1160 - 1166.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Neben, A. Korshunov, A. Benner, G. Wrobel, M. Hahn, F. Kokocinski, A. Golanov, S. Joos, and P. Lichter
Microarray-Based Screening for Molecular Markers in Medulloblastoma Revealed STK15 as Independent Predictor for Survival
Cancer Res., May 1, 2004; 64(9): 3103 - 3111.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. L. Grand, T. J. Powell, R. B. Nagle, D. J. Bearss, D. Tye, M. Gleason-Guzman, and L. H. Hurley
Mutations in the G-quadruplex silencer element and their relationship to c-MYC overexpression, NM23 repression, and therapeutic rescue
PNAS, April 20, 2004; 101(16): 6140 - 6145.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. A. Ginos, G. P. Page, B. S. Michalowicz, K. J. Patel, S. E. Volker, S. E. Pambuccian, F. G. Ondrey, G. L. Adams, and P. M. Gaffney
Identification of a Gene Expression Signature Associated with Recurrent Disease in Squamous Cell Carcinoma of the Head and Neck
Cancer Res., January 1, 2004; 64(1): 55 - 63.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Freier, K.
Right arrow Articles by Hofele, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Freier, K.
Right arrow Articles by Hofele, C.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online