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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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Immunohistochemical staining for cyclin D1, cortactin and FADD. A case without amplification and low cyclin D1 (A), FADD (B) and cortactin (C) expression and a case with amplification and high expression of cyclin D1 (E), FADD (F) and cortactin (G). Expression of ki-67 was unrelated to expression of the 11q13.3 genes (D, H).
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fig1: Immunohistochemical staining for cyclin D1, cortactin and FADD. A case without amplification and low cyclin D1 (A), FADD (B) and cortactin (C) expression and a case with amplification and high expression of cyclin D1 (E), FADD (F) and cortactin (G). Expression of ki-67 was unrelated to expression of the 11q13.3 genes (D, H).

Mentions: To study which gene within the 11q13. 3 region is responsible for the clinical outcome, we evaluated the expression of cyclin D1, FADD and cortactin using a series of 106 LSSCs previously stained for FADD expression (Table 1 and Figure 1). The other four consistently overexpressed genes in the 11q13 amplicon (Gibcus et al, 2007b) were not investigated further because no antibodies were available (TAOS1 and FLJ42258) or appeared to be inappropriate for immunohistochemistry on archive material (PPFIA1 and FGF19) (data not shown). Firstly, we determined whether there was a link between amplification and protein expression. For this purpose we immunostained a subset of 16 cases in which amplification was determined previously (Gibcus et al, 2007a). Carcinomas with 11q13 amplification showed high protein expression levels in 8/8 cases for cyclin D1, 8/9 cases for FADD and 8/9 for cortactin (Table 2). In addition, the high expression of cyclin D1 and cortactin in 5/8 and 3/7 cases without amplification, respectively, and FADD only in 1/7 suggest that FADD correlates best with amplification (Table 2). The frequencies of high expression without amplification indicate that increased expression of cyclin D1 and cortactin are caused by mechanisms other than amplification.


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)

Immunohistochemical staining for cyclin D1, cortactin and FADD. A case without amplification and low cyclin D1 (A), FADD (B) and cortactin (C) expression and a case with amplification and high expression of cyclin D1 (E), FADD (F) and cortactin (G). Expression of ki-67 was unrelated to expression of the 11q13.3 genes (D, H).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Immunohistochemical staining for cyclin D1, cortactin and FADD. A case without amplification and low cyclin D1 (A), FADD (B) and cortactin (C) expression and a case with amplification and high expression of cyclin D1 (E), FADD (F) and cortactin (G). Expression of ki-67 was unrelated to expression of the 11q13.3 genes (D, H).
Mentions: To study which gene within the 11q13. 3 region is responsible for the clinical outcome, we evaluated the expression of cyclin D1, FADD and cortactin using a series of 106 LSSCs previously stained for FADD expression (Table 1 and Figure 1). The other four consistently overexpressed genes in the 11q13 amplicon (Gibcus et al, 2007b) were not investigated further because no antibodies were available (TAOS1 and FLJ42258) or appeared to be inappropriate for immunohistochemistry on archive material (PPFIA1 and FGF19) (data not shown). Firstly, we determined whether there was a link between amplification and protein expression. For this purpose we immunostained a subset of 16 cases in which amplification was determined previously (Gibcus et al, 2007a). Carcinomas with 11q13 amplification showed high protein expression levels in 8/8 cases for cyclin D1, 8/9 cases for FADD and 8/9 for cortactin (Table 2). In addition, the high expression of cyclin D1 and cortactin in 5/8 and 3/7 cases without amplification, respectively, and FADD only in 1/7 suggest that FADD correlates best with amplification (Table 2). The frequencies of high expression without amplification indicate that increased expression of cyclin D1 and cortactin are caused by mechanisms other than amplification.

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