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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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EGFR protein and gene status in clear cell renal cell carcinoma. Immunohistochemical expression of EGFR protein, shown at lower (×10) and higher magnification (×20), was designated as discontinuous or continuous membrane staining of different intensity: (a) weak and moderate (+/++) discontinuous and continuous membrane immunostaining, and (b) strong continuous immunostaining (+++);. (c) chromosome 7 copy number was analyzed in tumor cells using fluorescence in situ hybridization (FISH) with an α-satellite DNA probe for chromosome 7 (centromere 7, green signal; EGFR gene, red signal); tumor nuclei showed disomy of chromosome 7 without EGFR gene amplification (d) tumor nuclei showed polysomy with a greater number of red and green signals than in normal cells; (c and d magnification × 100).
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Figure 1: EGFR protein and gene status in clear cell renal cell carcinoma. Immunohistochemical expression of EGFR protein, shown at lower (×10) and higher magnification (×20), was designated as discontinuous or continuous membrane staining of different intensity: (a) weak and moderate (+/++) discontinuous and continuous membrane immunostaining, and (b) strong continuous immunostaining (+++);. (c) chromosome 7 copy number was analyzed in tumor cells using fluorescence in situ hybridization (FISH) with an α-satellite DNA probe for chromosome 7 (centromere 7, green signal; EGFR gene, red signal); tumor nuclei showed disomy of chromosome 7 without EGFR gene amplification (d) tumor nuclei showed polysomy with a greater number of red and green signals than in normal cells; (c and d magnification × 100).

Mentions: EGFR staining patterns were designated as cytoplasmic or membranous. The membranous pattern was further classified as partial (discontinuous) (Figure 1a) or circumferential (continuous) (Figure 1b) membrane positivity, while staining intensity was graded as 0 for negative, 1+ for weak, 2+ for moderate, and 3+ for strong staining. Evaluation of immunohistochemical staining was based on histo score (H-score) that was calculated by multiplying the intensity of EGFR staining with percentage of tumor cells showing particular membranous staining pattern [15]. Continuous H-score (cH-score) was considered for only continuous (circumferential) staining of cell membrane, while total H-score (tH-score) included any membrane staining (continuous and discontinuous). For the purpose of two-way statistical analysis, H-score was determined as "low" or "high" using the median as the cut-off value. The evaluation of immunostaining was performed by one pathologist (G. Đ.), who was blinded for clinical data. On statistical analysis, the mean value of immunohistochemical staining of two tissue microarrays was used.


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)

EGFR protein and gene status in clear cell renal cell carcinoma. Immunohistochemical expression of EGFR protein, shown at lower (×10) and higher magnification (×20), was designated as discontinuous or continuous membrane staining of different intensity: (a) weak and moderate (+/++) discontinuous and continuous membrane immunostaining, and (b) strong continuous immunostaining (+++);. (c) chromosome 7 copy number was analyzed in tumor cells using fluorescence in situ hybridization (FISH) with an α-satellite DNA probe for chromosome 7 (centromere 7, green signal; EGFR gene, red signal); tumor nuclei showed disomy of chromosome 7 without EGFR gene amplification (d) tumor nuclei showed polysomy with a greater number of red and green signals than in normal cells; (c and d magnification × 100).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: EGFR protein and gene status in clear cell renal cell carcinoma. Immunohistochemical expression of EGFR protein, shown at lower (×10) and higher magnification (×20), was designated as discontinuous or continuous membrane staining of different intensity: (a) weak and moderate (+/++) discontinuous and continuous membrane immunostaining, and (b) strong continuous immunostaining (+++);. (c) chromosome 7 copy number was analyzed in tumor cells using fluorescence in situ hybridization (FISH) with an α-satellite DNA probe for chromosome 7 (centromere 7, green signal; EGFR gene, red signal); tumor nuclei showed disomy of chromosome 7 without EGFR gene amplification (d) tumor nuclei showed polysomy with a greater number of red and green signals than in normal cells; (c and d magnification × 100).
Mentions: EGFR staining patterns were designated as cytoplasmic or membranous. The membranous pattern was further classified as partial (discontinuous) (Figure 1a) or circumferential (continuous) (Figure 1b) membrane positivity, while staining intensity was graded as 0 for negative, 1+ for weak, 2+ for moderate, and 3+ for strong staining. Evaluation of immunohistochemical staining was based on histo score (H-score) that was calculated by multiplying the intensity of EGFR staining with percentage of tumor cells showing particular membranous staining pattern [15]. Continuous H-score (cH-score) was considered for only continuous (circumferential) staining of cell membrane, while total H-score (tH-score) included any membrane staining (continuous and discontinuous). For the purpose of two-way statistical analysis, H-score was determined as "low" or "high" using the median as the cut-off value. The evaluation of immunostaining was performed by one pathologist (G. Đ.), who was blinded for clinical data. On statistical analysis, the mean value of immunohistochemical staining of two tissue microarrays was used.

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