Background: Endometrial stromal sarcomas (ESS) are rare neoplasms, which are currently classified in low grade ESS, with indolent growth, tendency to local recurrences and, more rarely, to metastasize, and undifferentiated endometrial sarcomas (UES), with a very aggressive behavior. Recently, Epidermal Growth Factor Receptor (EGFR) expression has been described in a large series of ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. Aim of our study was to analyze EGFR immunohistochemical expression and EGFR gene amplification by FISH in a series of ESS. Design: EGFR status was investigated in 10 ESS, including 7 low-grade ESS and 3 undifferentiated ESS. EGFR expression levels were assessed by immunohistochemistry with Dako EGFRpharmDX kit (DAKO, Glostrup, Denmark). Staining intensity and percentage of positive cells were scored for each case. Gene amplification analysis was performed with Dual-Color Fluorescence In Situ Hybridization (FISH) (Vysis, Downers Grove, IL, USA), with specific probes for EGFR gene (LSI Spectrum Orange) and Chromosome 7 centromeric region (CEP 7 Spectrum Green). At least 50 neoplastic nuclei for each case were scored for both grewen and orange signals, and the ratio EGFR/CEP7 was evaluated. Only cases with ratios of 2 or higher were considered amplified. Results: Nine out of 10 (90%) ESS showed positive immunostaining. Six out of seven low-grade variants were positive, showing both cytoplasmic and membranous (5 cases) or only membranous staining (1 case). The staining intensity was interpreted as 3+ (3 cases), or 2+ (3 cases), with percentages of positive cells ranging from 60 to 80%. All three cases of UES were positive for EGFR, with membranous and cytoplasmic (2 cases) or only membranous (1 case) staining. The staining intensity was evaluated as 1+, 2+ and 3+, with percentages of positive tumor cells ranging from 50 % to 80%. FISH analysis showed EGFR/CEP7 ratios constantly below the cut-off value, ranging from 0.9 to 1.3. Conclusions: Our study confirms that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, thus EGFR over-expression in ESS should be related to different genetic mechanisms. Further studies are needed to identify specific EGFR genetic abnormalities, potentially useful to select patients who might benefit from current EGFR-targeted therapeutic options.

Analysis of EGFR status in endometrial stromal sarcoma / COSSU ROCCA, Paolo Alessandro; Pili, F; Festa, A; Contini, M; Mura, Antonica; Bosincu, L; Brunelli, M; Martignoni, G; Massareli, G.. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - 87:Supplement(2007), pp. 193A-194A. ((Intervento presentato al convegno USCAP 96TH ANNUAL MEETING tenutosi a SAN DIEGO (CA). nel MARCH 24-30 2007.

Analysis of EGFR status in endometrial stromal sarcoma

COSSU ROCCA, Paolo Alessandro;MURA, Antonica;
2007

Abstract

Background: Endometrial stromal sarcomas (ESS) are rare neoplasms, which are currently classified in low grade ESS, with indolent growth, tendency to local recurrences and, more rarely, to metastasize, and undifferentiated endometrial sarcomas (UES), with a very aggressive behavior. Recently, Epidermal Growth Factor Receptor (EGFR) expression has been described in a large series of ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. Aim of our study was to analyze EGFR immunohistochemical expression and EGFR gene amplification by FISH in a series of ESS. Design: EGFR status was investigated in 10 ESS, including 7 low-grade ESS and 3 undifferentiated ESS. EGFR expression levels were assessed by immunohistochemistry with Dako EGFRpharmDX kit (DAKO, Glostrup, Denmark). Staining intensity and percentage of positive cells were scored for each case. Gene amplification analysis was performed with Dual-Color Fluorescence In Situ Hybridization (FISH) (Vysis, Downers Grove, IL, USA), with specific probes for EGFR gene (LSI Spectrum Orange) and Chromosome 7 centromeric region (CEP 7 Spectrum Green). At least 50 neoplastic nuclei for each case were scored for both grewen and orange signals, and the ratio EGFR/CEP7 was evaluated. Only cases with ratios of 2 or higher were considered amplified. Results: Nine out of 10 (90%) ESS showed positive immunostaining. Six out of seven low-grade variants were positive, showing both cytoplasmic and membranous (5 cases) or only membranous staining (1 case). The staining intensity was interpreted as 3+ (3 cases), or 2+ (3 cases), with percentages of positive cells ranging from 60 to 80%. All three cases of UES were positive for EGFR, with membranous and cytoplasmic (2 cases) or only membranous (1 case) staining. The staining intensity was evaluated as 1+, 2+ and 3+, with percentages of positive tumor cells ranging from 50 % to 80%. FISH analysis showed EGFR/CEP7 ratios constantly below the cut-off value, ranging from 0.9 to 1.3. Conclusions: Our study confirms that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, thus EGFR over-expression in ESS should be related to different genetic mechanisms. Further studies are needed to identify specific EGFR genetic abnormalities, potentially useful to select patients who might benefit from current EGFR-targeted therapeutic options.
Analysis of EGFR status in endometrial stromal sarcoma / COSSU ROCCA, Paolo Alessandro; Pili, F; Festa, A; Contini, M; Mura, Antonica; Bosincu, L; Brunelli, M; Martignoni, G; Massareli, G.. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - 87:Supplement(2007), pp. 193A-194A. ((Intervento presentato al convegno USCAP 96TH ANNUAL MEETING tenutosi a SAN DIEGO (CA). nel MARCH 24-30 2007.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/66527
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