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Cortactin expression predicts poor survival in laryngeal carcinoma.

Gibcus JH, Mastik MF, Menkema L, de Bock GH, Kluin PM, Schuuring E, van der Wal JE - Br. J. Cancer (2008)

Bottom Line: Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality.Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD.Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

ABSTRACT
Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

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Kaplan–Meier analysis on disease-specific mortality for cortactin (A), lymph node positivity (B) and cortactin positivity within lymph node-positive cases (C). Remaining cases are shown below the plots.
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fig2: Kaplan–Meier analysis on disease-specific mortality for cortactin (A), lymph node positivity (B) and cortactin positivity within lymph node-positive cases (C). Remaining cases are shown below the plots.

Mentions: A multivariate Cox regression model including cortactin, cyclin D1, FADD, treatment and lymph node metastasis showed that cortactin expression (HR=8.46; 95% CI, 1.63–43.88; P=0.011) and lymph node metastasis (HR=3.96; 95% CI, 1.30–12.06; P=0.015) were predictors for increased DSM, whereas FADD and cyclin D1 were not (Table 4A). Furthermore, in the multivariate analysis treatment with surgery, radiotherapy or a combination of both was not related to increased DSM (Table 4A). To assess whether cortactin and lymph node metastasis were independent prognostic factors, a multivariate Cox regression, using only cortactin expression and lymph node metastasis, was performed. Both cortactin expression and lymph node metastasis were significantly related to increased DSM (Table 4B), implying they are both prognostic factors. However, Kaplan–Meier analysis for cortactin, within lymph node positive tumours only, revealed a remarkable difference (Log-rank: P=0.00002) in DSM between cortactin-positive and cortactin-negative cases (Figure 2).


Cortactin expression predicts poor survival in laryngeal carcinoma.

Gibcus JH, Mastik MF, Menkema L, de Bock GH, Kluin PM, Schuuring E, van der Wal JE - Br. J. Cancer (2008)

Kaplan–Meier analysis on disease-specific mortality for cortactin (A), lymph node positivity (B) and cortactin positivity within lymph node-positive cases (C). Remaining cases are shown below the plots.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266851&req=5

fig2: Kaplan–Meier analysis on disease-specific mortality for cortactin (A), lymph node positivity (B) and cortactin positivity within lymph node-positive cases (C). Remaining cases are shown below the plots.
Mentions: A multivariate Cox regression model including cortactin, cyclin D1, FADD, treatment and lymph node metastasis showed that cortactin expression (HR=8.46; 95% CI, 1.63–43.88; P=0.011) and lymph node metastasis (HR=3.96; 95% CI, 1.30–12.06; P=0.015) were predictors for increased DSM, whereas FADD and cyclin D1 were not (Table 4A). Furthermore, in the multivariate analysis treatment with surgery, radiotherapy or a combination of both was not related to increased DSM (Table 4A). To assess whether cortactin and lymph node metastasis were independent prognostic factors, a multivariate Cox regression, using only cortactin expression and lymph node metastasis, was performed. Both cortactin expression and lymph node metastasis were significantly related to increased DSM (Table 4B), implying they are both prognostic factors. However, Kaplan–Meier analysis for cortactin, within lymph node positive tumours only, revealed a remarkable difference (Log-rank: P=0.00002) in DSM between cortactin-positive and cortactin-negative cases (Figure 2).

Bottom Line: Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality.Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD.Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

ABSTRACT
Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

Show MeSH
Related in: MedlinePlus