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EGFR protein overexpression correlates with chromosome 7 polysomy and poor prognostic parameters in clear cell renal cell carcinoma.

Dorđević G, Matušan Ilijaš K, Hadžisejdić I, Maričić A, Grahovac B, Jonjić N - J. Biomed. Sci. (2012)

Bottom Line: The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC).FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression.In conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, School of Medicine, University of Rijeka, B, Branchetta 20, Rijeka 51000, Croatia.

ABSTRACT

Background: The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). The present study was designed to analyze more objectively the protein EGFR expression in CCRCC and to compare its value with EGFR gene copy number changes and clinicopathologic characteristics including patient survival.

Methods: The protein EGFR expression was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR staining.

Results: Membrane EGFR expression in tumor cells was heterogeneous with respect to the proportion of positive cells and staining intensity. FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression. Moreover, EGFR overexpression was associated with a higher nuclear grade, larger tumor size and shorter patient's survival, while there was no connection with pathological stage.

Conclusion: In conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

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Chromosome 7 polysomy in different groups of clear cell renal cell carcinoma (CCRCC) regarding EGFR immunohistochemical staining intensity: (a) the number of tumors categorised as polysomic decreases with attenuation of staining intensity (p = 0.019, Pearson's χ2-test). Black bars represent percentage of tumors with chromosome 7 polysomy, white bars represent percentage of tumors without chromosome 7 polysomy; (b) the number of tumor cells showing chromosome 7 polysomy is declining with attenuation of EGFR immunohistochemical staining (p = 0.004, one-way ANOVA).
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Figure 2: Chromosome 7 polysomy in different groups of clear cell renal cell carcinoma (CCRCC) regarding EGFR immunohistochemical staining intensity: (a) the number of tumors categorised as polysomic decreases with attenuation of staining intensity (p = 0.019, Pearson's χ2-test). Black bars represent percentage of tumors with chromosome 7 polysomy, white bars represent percentage of tumors without chromosome 7 polysomy; (b) the number of tumor cells showing chromosome 7 polysomy is declining with attenuation of EGFR immunohistochemical staining (p = 0.004, one-way ANOVA).

Mentions: FISH analysis did not reveal any amplification of EGFR gene in our cohort of CCRCC, while polysomy was detected in 17 of 41 examined tumors (41.5%) (Figure 1c and 1d). Chromosome 7 polysomy was found to be associated with EGFR immunohistochemical expression (Figure 2 and 3). The proportion of tumors showing chromosome 7 polysomy was increasing with EGFR staining intensity (p = 0.019) (Figure 2a). The EGFR staining intensity was also related to the number of tumor cells with chromosome 7 polysomy (p = 0.004) (Figure 2b).


EGFR protein overexpression correlates with chromosome 7 polysomy and poor prognostic parameters in clear cell renal cell carcinoma.

Dorđević G, Matušan Ilijaš K, Hadžisejdić I, Maričić A, Grahovac B, Jonjić N - J. Biomed. Sci. (2012)

Chromosome 7 polysomy in different groups of clear cell renal cell carcinoma (CCRCC) regarding EGFR immunohistochemical staining intensity: (a) the number of tumors categorised as polysomic decreases with attenuation of staining intensity (p = 0.019, Pearson's χ2-test). Black bars represent percentage of tumors with chromosome 7 polysomy, white bars represent percentage of tumors without chromosome 7 polysomy; (b) the number of tumor cells showing chromosome 7 polysomy is declining with attenuation of EGFR immunohistochemical staining (p = 0.004, one-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368721&req=5

Figure 2: Chromosome 7 polysomy in different groups of clear cell renal cell carcinoma (CCRCC) regarding EGFR immunohistochemical staining intensity: (a) the number of tumors categorised as polysomic decreases with attenuation of staining intensity (p = 0.019, Pearson's χ2-test). Black bars represent percentage of tumors with chromosome 7 polysomy, white bars represent percentage of tumors without chromosome 7 polysomy; (b) the number of tumor cells showing chromosome 7 polysomy is declining with attenuation of EGFR immunohistochemical staining (p = 0.004, one-way ANOVA).
Mentions: FISH analysis did not reveal any amplification of EGFR gene in our cohort of CCRCC, while polysomy was detected in 17 of 41 examined tumors (41.5%) (Figure 1c and 1d). Chromosome 7 polysomy was found to be associated with EGFR immunohistochemical expression (Figure 2 and 3). The proportion of tumors showing chromosome 7 polysomy was increasing with EGFR staining intensity (p = 0.019) (Figure 2a). The EGFR staining intensity was also related to the number of tumor cells with chromosome 7 polysomy (p = 0.004) (Figure 2b).

Bottom Line: The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC).FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression.In conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, School of Medicine, University of Rijeka, B, Branchetta 20, Rijeka 51000, Croatia.

ABSTRACT

Background: The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). The present study was designed to analyze more objectively the protein EGFR expression in CCRCC and to compare its value with EGFR gene copy number changes and clinicopathologic characteristics including patient survival.

Methods: The protein EGFR expression was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR staining.

Results: Membrane EGFR expression in tumor cells was heterogeneous with respect to the proportion of positive cells and staining intensity. FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression. Moreover, EGFR overexpression was associated with a higher nuclear grade, larger tumor size and shorter patient's survival, while there was no connection with pathological stage.

Conclusion: In conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

Show MeSH
Related in: MedlinePlus