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MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer.

Fountzilas G, Kalogera-Fountzila A, Lambaki S, Wirtz RM, Nikolaou A, Karayannopoulou G, Bobos M, Kotoula V, Murray S, Lambropoulos A, Aravantinos G, Markou K, Athanassiou E, Misailidou D, Kalogeras KT, Skarlos D - J Oncol (2009)

Bottom Line: In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response.In conclusion, CCRT is feasible and active.However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

ABSTRACT
Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT). We identified 37 patients treated with this approach, of which 13 (35%) achieved a complete response and 10 (27%) achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

No MeSH data available.


Related in: MedlinePlus

Fluorescence in situ hybridization with gene and centromeric specific probes. (a) and (b) Neoplastic nuclei showing polysomy of chromosome 7 (CEP7, green signals) and EGFR high level gene gain (red signals, arrowheads); (c) Neoplastic nuclei showing trisomy or polysomy of the MET gene (red signals) and SE7 (green signals); (d) Representative area from a case without genetic alterations. The majority of the neoplastic nuclei have 2 copies of the MET gene and SE7; (e) High polysomy of the D7S486 locus (red signals); (f) Deletion of the D7S486 gene locus in tumor cells, as defined by the presence of a single gene locus probe signal (red signals) and two CEP7 signals (green signals), or by the simultaneous lack of both of the gene locus signals and the presence of CEP7 signals (hemizygous and homozygous deletion, resp.).
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fig3: Fluorescence in situ hybridization with gene and centromeric specific probes. (a) and (b) Neoplastic nuclei showing polysomy of chromosome 7 (CEP7, green signals) and EGFR high level gene gain (red signals, arrowheads); (c) Neoplastic nuclei showing trisomy or polysomy of the MET gene (red signals) and SE7 (green signals); (d) Representative area from a case without genetic alterations. The majority of the neoplastic nuclei have 2 copies of the MET gene and SE7; (e) High polysomy of the D7S486 locus (red signals); (f) Deletion of the D7S486 gene locus in tumor cells, as defined by the presence of a single gene locus probe signal (red signals) and two CEP7 signals (green signals), or by the simultaneous lack of both of the gene locus signals and the presence of CEP7 signals (hemizygous and homozygous deletion, resp.).

Mentions: Individual EGFR, ERCC1, MET, p16INK4A, and p-53 IHC and FISH data along with selected patient characteristics and responses are presented in Tables 3 and 4. In summary, thirty-one of 32 tumor samples (97%) were found to be EGFR positive, while in 22 samples (69%) EGFR was overexpressed (Figures 2(a) and 2(b)). No association between EGFR overexpression and complete response was identified (9/22 CRs among patients with EGFR overexpression versus 2/10 CRs among patients without EGFR overexpression; P = .425). One sample was EGFR amplified (Figures 3(a) and 3(b)).


MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer.

Fountzilas G, Kalogera-Fountzila A, Lambaki S, Wirtz RM, Nikolaou A, Karayannopoulou G, Bobos M, Kotoula V, Murray S, Lambropoulos A, Aravantinos G, Markou K, Athanassiou E, Misailidou D, Kalogeras KT, Skarlos D - J Oncol (2009)

Fluorescence in situ hybridization with gene and centromeric specific probes. (a) and (b) Neoplastic nuclei showing polysomy of chromosome 7 (CEP7, green signals) and EGFR high level gene gain (red signals, arrowheads); (c) Neoplastic nuclei showing trisomy or polysomy of the MET gene (red signals) and SE7 (green signals); (d) Representative area from a case without genetic alterations. The majority of the neoplastic nuclei have 2 copies of the MET gene and SE7; (e) High polysomy of the D7S486 locus (red signals); (f) Deletion of the D7S486 gene locus in tumor cells, as defined by the presence of a single gene locus probe signal (red signals) and two CEP7 signals (green signals), or by the simultaneous lack of both of the gene locus signals and the presence of CEP7 signals (hemizygous and homozygous deletion, resp.).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801452&req=5

fig3: Fluorescence in situ hybridization with gene and centromeric specific probes. (a) and (b) Neoplastic nuclei showing polysomy of chromosome 7 (CEP7, green signals) and EGFR high level gene gain (red signals, arrowheads); (c) Neoplastic nuclei showing trisomy or polysomy of the MET gene (red signals) and SE7 (green signals); (d) Representative area from a case without genetic alterations. The majority of the neoplastic nuclei have 2 copies of the MET gene and SE7; (e) High polysomy of the D7S486 locus (red signals); (f) Deletion of the D7S486 gene locus in tumor cells, as defined by the presence of a single gene locus probe signal (red signals) and two CEP7 signals (green signals), or by the simultaneous lack of both of the gene locus signals and the presence of CEP7 signals (hemizygous and homozygous deletion, resp.).
Mentions: Individual EGFR, ERCC1, MET, p16INK4A, and p-53 IHC and FISH data along with selected patient characteristics and responses are presented in Tables 3 and 4. In summary, thirty-one of 32 tumor samples (97%) were found to be EGFR positive, while in 22 samples (69%) EGFR was overexpressed (Figures 2(a) and 2(b)). No association between EGFR overexpression and complete response was identified (9/22 CRs among patients with EGFR overexpression versus 2/10 CRs among patients without EGFR overexpression; P = .425). One sample was EGFR amplified (Figures 3(a) and 3(b)).

Bottom Line: In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response.In conclusion, CCRT is feasible and active.However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

ABSTRACT
Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT). We identified 37 patients treated with this approach, of which 13 (35%) achieved a complete response and 10 (27%) achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

No MeSH data available.


Related in: MedlinePlus