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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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Kaplan-Meier survival analysis according to EGFR protein expression determined as H-score of continuous immunohistochemical staining (cH-score) and total immunohistochemical staining (tH-score) in clear cell renal cell carcinoma (CCRCC): (a) The log-rank test showed significantly shorter overall survival in patients with tumors showing high continuous EGFR protein expression that was above median H-score values (p = 0.046). The 5-year survival rate was 59% for patients whose tumors showed low EGFR cH-score vs. 40% for patients whose tumors showed high EGFR cH-score; (b) on the contrary, the log-rank test showed no significant association between EGFR tH-score and survival (p = 0.074). The 5-year survival rate was 57% for patients whose tumors showed low EGFR tH-score and 40% for patients whose tumors showed high EGFR tH-score.
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Figure 4: Kaplan-Meier survival analysis according to EGFR protein expression determined as H-score of continuous immunohistochemical staining (cH-score) and total immunohistochemical staining (tH-score) in clear cell renal cell carcinoma (CCRCC): (a) The log-rank test showed significantly shorter overall survival in patients with tumors showing high continuous EGFR protein expression that was above median H-score values (p = 0.046). The 5-year survival rate was 59% for patients whose tumors showed low EGFR cH-score vs. 40% for patients whose tumors showed high EGFR cH-score; (b) on the contrary, the log-rank test showed no significant association between EGFR tH-score and survival (p = 0.074). The 5-year survival rate was 57% for patients whose tumors showed low EGFR tH-score and 40% for patients whose tumors showed high EGFR tH-score.

Mentions: EGFR immunoexpression analysis showed association of high %, tH-score and cH- score values with a higher nuclear grade (p < 0.001, p < 0.001 and p = 0.006, respectively) and larger tumors (p = 0.011, p = 0.002 and p = 0.01, respectively), while there was no association with pathological T stage (Table 2). On contrary, chromosome 7 polysomy showed no association with any clinicopathological feature as well as patients' survival. EGFR protein expression showed relationship with patient survival (Figure 4). Log-rank test showed an association between shorter patient survival and high EGFR protein expression only for continuous membranous EGFR staining (p = 0.046), while it could not be found for total membranous staining (p = 0.074) and % of EGFR membranous staining (p = 0.168). Association of EGFR cH-score and tH-score with cumulative proportion of patients surviving during the follow-up are shown in Figure 4. Univariate survival analysis also showed nuclear grade and pathological T stage to be significant predictive factors (p < 0.001 and p = 0.003, respectively). However, on multivariate analysis, only nuclear grade remained significant (p = 0.002, relative risk 3, 95% confidence interval 1.7-5.3), while pathologic stage (p = 0.009, relative risk 1.5, 95% confidence interval 1-2.4) together with EGFR protein expression (p = 0.175, relative risk 1.3, 95% confidence interval 0.9-1.9) showed no independent prognostic value.


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)

Kaplan-Meier survival analysis according to EGFR protein expression determined as H-score of continuous immunohistochemical staining (cH-score) and total immunohistochemical staining (tH-score) in clear cell renal cell carcinoma (CCRCC): (a) The log-rank test showed significantly shorter overall survival in patients with tumors showing high continuous EGFR protein expression that was above median H-score values (p = 0.046). The 5-year survival rate was 59% for patients whose tumors showed low EGFR cH-score vs. 40% for patients whose tumors showed high EGFR cH-score; (b) on the contrary, the log-rank test showed no significant association between EGFR tH-score and survival (p = 0.074). The 5-year survival rate was 57% for patients whose tumors showed low EGFR tH-score and 40% for patients whose tumors showed high EGFR tH-score.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Kaplan-Meier survival analysis according to EGFR protein expression determined as H-score of continuous immunohistochemical staining (cH-score) and total immunohistochemical staining (tH-score) in clear cell renal cell carcinoma (CCRCC): (a) The log-rank test showed significantly shorter overall survival in patients with tumors showing high continuous EGFR protein expression that was above median H-score values (p = 0.046). The 5-year survival rate was 59% for patients whose tumors showed low EGFR cH-score vs. 40% for patients whose tumors showed high EGFR cH-score; (b) on the contrary, the log-rank test showed no significant association between EGFR tH-score and survival (p = 0.074). The 5-year survival rate was 57% for patients whose tumors showed low EGFR tH-score and 40% for patients whose tumors showed high EGFR tH-score.
Mentions: EGFR immunoexpression analysis showed association of high %, tH-score and cH- score values with a higher nuclear grade (p < 0.001, p < 0.001 and p = 0.006, respectively) and larger tumors (p = 0.011, p = 0.002 and p = 0.01, respectively), while there was no association with pathological T stage (Table 2). On contrary, chromosome 7 polysomy showed no association with any clinicopathological feature as well as patients' survival. EGFR protein expression showed relationship with patient survival (Figure 4). Log-rank test showed an association between shorter patient survival and high EGFR protein expression only for continuous membranous EGFR staining (p = 0.046), while it could not be found for total membranous staining (p = 0.074) and % of EGFR membranous staining (p = 0.168). Association of EGFR cH-score and tH-score with cumulative proportion of patients surviving during the follow-up are shown in Figure 4. Univariate survival analysis also showed nuclear grade and pathological T stage to be significant predictive factors (p < 0.001 and p = 0.003, respectively). However, on multivariate analysis, only nuclear grade remained significant (p = 0.002, relative risk 3, 95% confidence interval 1.7-5.3), while pathologic stage (p = 0.009, relative risk 1.5, 95% confidence interval 1-2.4) together with EGFR protein expression (p = 0.175, relative risk 1.3, 95% confidence interval 0.9-1.9) showed no independent prognostic value.

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